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Sample records for nuclear protein export

  1. Adducin family proteins possess different nuclear export potentials.

    Science.gov (United States)

    Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

    2017-05-10

    The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ( 377 FEALMRMLDWLGYRT 391 ) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

  2. Nuclear localization signal regulates porcine circovirus type 2 capsid protein nuclear export through phosphorylation.

    Science.gov (United States)

    Hou, Qiang; Hou, Shaohua; Chen, Qing; Jia, Hong; Xin, Ting; Jiang, Yitong; Guo, Xiaoyu; Zhu, Hongfei

    2018-02-15

    The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. RanBP3 influences interactions between CRM1 and its nuclear protein export substrates

    OpenAIRE

    Englmeier, Ludwig; Fornerod, Maarten; Bischoff, F. Ralf; Petosa, Carlo; Mattaj, Iain W.; Kutay, Ulrike

    2001-01-01

    We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1 family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP. However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can stabilize CRM1–export substrate interaction. Nuclear RanBP3 stimulates CRM1-dependent protein export in permeabilized cells. These data indicate that RanBP3 functions by a novel mec...

  4. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

    Science.gov (United States)

    Finn, Erin M.; DeRoo, Elise P.; Clement, George W.; Rao, Sheila; Kruse, Sarah E.; Kokanovich, Kate M.; Belanger, Kenneth D.

    2013-01-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export. PMID:23295456

  5. The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export.

    Science.gov (United States)

    Brunotte, Linda; Flies, Joe; Bolte, Hardin; Reuther, Peter; Vreede, Frank; Schwemmle, Martin

    2014-07-18

    In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. The BRO proteins of Bombyx mori nucleopolyhedrovirus are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

    International Nuclear Information System (INIS)

    Kang, Won Kyung; Kurihara, Masaaki; Matsumoto, Shogo

    2006-01-01

    The BRO proteins of Bombyx mori nucleopolyhedrovirus (BmNPV) display a biphasic pattern of intracellular localization during infection. At early times, they reside in the nucleus but then show both cytoplasmic and nuclear localization as the infection proceeds. Therefore, we examined the possibility of nuclear export. Using inhibitors, we reveal that BmNPV BRO proteins shuttle between the nucleus and cytoplasm. Mutations on the leucine-rich region of BRO proteins resulted in nuclear accumulation of transiently expressed proteins, suggesting that this region functions as a CRM1-dependent nuclear export signal (NES). On the contrary, mutant BRO-D with an altered NES did not show nuclear accumulation in infected cells, although protein production seemed to be reduced. RT-PCR analysis showed that the lower level of protein production was due to a reduction in RNA synthesis. Taken together, our results suggest that BRO proteins are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

  7. Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.

    Science.gov (United States)

    Li, Ping; Noegel, Angelika A

    2015-11-16

    Nuclear export of messenger ribonucleoproteins (mRNPs) through the nuclear pore complex (NPC) can be roughly classified into two forms: bulk and specific export, involving an nuclear RNA export factor 1 (NXF1)-dependent pathway and chromosome region maintenance 1 (CRM1)-dependent pathway, respectively. SUN proteins constitute the inner nuclear envelope component of the l I: nker of N: ucleoskeleton and C: ytoskeleton (LINC) complex. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results indicate that both SUN1 and SUN2 interact with heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. Leptomycin B treatment indicates that SUN1 functions in mammalian mRNA export involving the NXF1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complexes via a direct interaction with NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope and hands it over to Nup153. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus

    International Nuclear Information System (INIS)

    Munoz-Fontela, C.; Collado, M.; Rodriguez, E.; Garcia, M.A.; Alvarez-Barrientos, A.; Arroyo, J.; Nombela, C.; Rivas, C.

    2005-01-01

    LANA2 is a latent protein detected in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected B cells that inhibits p53-dependent transcriptional transactivation and apoptosis and PKR-dependent apoptosis, suggesting an important role in the transforming activity of the virus. It has been reported that LANA2 localizes into the nucleus of both KSHV-infected B cells and transiently transfected HeLa cells. In this study, we show that LANA2 is a nucleocytoplasmic shuttling protein that requires a Rev-type nuclear export signal located in the C-terminus to direct the protein to the cytoplasm, through an association with the export receptor CRM1. In addition, a functional protein kinase B (PKB)/Akt phosphorylation motif partially overlapping with the nuclear export signal was identified. Nuclear exclusion of LANA2 was negatively regulated by the phosphorylation of threonine 564 by Akt. The ability of LANA2 to shuttle between nucleus and cytoplasm has implications for the function of this viral protein

  9. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

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    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kondoh, Yasumitsu; Osada, Hiroyuki [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori [Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2017-07-15

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

  10. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

    International Nuclear Information System (INIS)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-01-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

  11. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

    Science.gov (United States)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-07-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA export.

    Science.gov (United States)

    Kristó, Ildikó; Bajusz, Csaba; Borsos, Barbara N; Pankotai, Tibor; Dopie, Joseph; Jankovics, Ferenc; Vartiainen, Maria K; Erdélyi, Miklós; Vilmos, Péter

    2017-10-01

    Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus. The distribution of Moesin in the nucleus suggests a function in transcription and the depletion of mRNA export factors Nup98 or its interacting partner, Rae1, leads to the nuclear accumulation of Moesin, suggesting that the nuclear function of the protein is linked to mRNA export. Moesin localizes to mRNP particles through the interaction with the mRNA export factor PCID2 and knock down of Moesin leads to the accumulation of mRNA in the nucleus. Based on our results we propose that, beyond its well-known, manifold functions in the cytoplasm, the ERM protein of Drosophila is a new, functional component of the nucleus where it participates in mRNA export. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import.

    Science.gov (United States)

    Jacobs, Susan C; Taylor, Adam; Herrero, Lara J; Mahalingam, Suresh; Fazakerley, John K

    2017-10-20

    Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export from the nucleus and a region within the N-terminal part of CHIKV capsid protein was required for active nuclear targeting. In contrast to encephalitic alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus. Interactions between capsid protein and the nucleus warrant further investigation.

  14. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

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    Andrea Cerutti

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS, but no nuclear export signal (NES has yet been identified.We show here that the aa(109-133 region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126 in the identified NES or in the sequence encoding the mature core aa(1-173 significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  15. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

    Science.gov (United States)

    Cerutti, Andrea; Maillard, Patrick; Minisini, Rosalba; Vidalain, Pierre-Olivier; Roohvand, Farzin; Pecheur, Eve-Isabelle; Pirisi, Mario; Budkowska, Agata

    2011-01-01

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified.We show here that the aa(109-133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1-173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  16. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  17. Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

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    Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

    2010-05-21

    NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

  18. Phosphorylation of zona occludens-2 by protein kinase C epsilon regulates its nuclear exportation.

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    Chamorro, David; Alarcón, Lourdes; Ponce, Arturo; Tapia, Rocio; González-Aguilar, Héctor; Robles-Flores, Martha; Mejía-Castillo, Teresa; Segovia, José; Bandala, Yamir; Juaristi, Eusebio; González-Mariscal, Lorenza

    2009-09-01

    Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens (ZO)-2. After transfection in sparse cells, 74% of cells exhibit ZO-2 at the nucleus, and after 18 h the value decreases to 17%. The mutation S369A located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Because Ser369 represents a putative protein kinase C (PKC) phosphorylation site, we tested the effect of PKC inhibition and stimulation on the nuclear export of ZO-2. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser369 by novel PKCepsilon. To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane. These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO-2.

  19. Optimizing the protein switch: altering nuclear import and export signals, and ligand binding domain

    Science.gov (United States)

    Kakar, Mudit; Davis, James R.; Kern, Steve E.; Lim, Carol S.

    2007-01-01

    Ligand regulated localization controllable protein constructs were optimized in this study. Several constructs were made from a classical nuclear export signal (HIV-rev, MAPKK, or progesterone receptor) in combination with a SV40 T-antigen type nuclear import signal. Different ligand binding domains (LBDs from glucocorticoid receptor or progesterone receptor) were also tested for their ability to impart control over localization of proteins. This study was designed to create constructs which are cytoplasmic in the absence of ligand and nuclear in the presence of ligand, and also to regulate the amount of protein translocating to the nucleus on ligand induction. The balance between the strengths of import and export signals was critical for overall localization of proteins. The amount of protein entering the nucleus was also affected by the dose of ligand (10-100nM). However, the overall import characteristics were determined by the strengths of localization signals and the inherent localization properties of the LBD used. This study established that the amount of protein present in a particular compartment can be regulated by the use of localization signals of various strengths. These optimized localization controllable protein constructs can be used to correct for diseases due to aberrant localization of proteins. PMID:17574289

  20. Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

    Science.gov (United States)

    Loftus, Kyle M; Cui, Heying; Coutavas, Elias; King, David S; Ceravolo, Amanda; Pereiras, Dylan; Solmaz, Sozanne R

    2017-08-03

    Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

  1. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins.

    Science.gov (United States)

    Aguilera, Cristina; Fernández-Majada, Vanessa; Inglés-Esteve, Julia; Rodilla, Verónica; Bigas, Anna; Espinosa, Lluís

    2006-09-01

    IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.

  2. Identification of a functional nuclear export signal in the green fluorescent protein asFP499

    International Nuclear Information System (INIS)

    Mustafa, Huseyin; Strasser, Bernd; Rauth, Sabine; Irving, Robert A.; Wark, Kim L.

    2006-01-01

    The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified 194 LRMEKLNI 201 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES

  3. Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion.

    Science.gov (United States)

    Alefantis, Timothy; Flaig, Katherine E; Wigdahl, Brian; Jain, Pooja

    2007-05-01

    Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-kappaB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.

  4. Nuclear export and import of human hepatitis B virus capsid protein and particles.

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Li

    Full Text Available It remains unclear what determines the subcellular localization of hepatitis B virus (HBV core protein (HBc and particles. To address this fundamental issue, we have identified four distinct HBc localization signals in the arginine rich domain (ARD of HBc, using immunofluorescence confocal microscopy and fractionation/Western blot analysis. ARD consists of four tight clustering arginine-rich subdomains. ARD-I and ARD-III are associated with two co-dependent nuclear localization signals (NLS, while ARD-II and ARD-IV behave like two independent nuclear export signals (NES. This conclusion is based on five independent lines of experimental evidence: i Using an HBV replication system in hepatoma cells, we demonstrated in a double-blind manner that only the HBc of mutant ARD-II+IV, among a total of 15 ARD mutants, can predominantly localize to the nucleus. ii These results were confirmed using a chimera reporter system by placing mutant or wild type HBc trafficking signals in the heterologous context of SV40 large T antigen (LT. iii By a heterokaryon or homokaryon analysis, the fusion protein of SV40 LT-HBc ARD appeared to transport from nuclei of transfected donor cells to nuclei of recipient cells, suggesting the existence of an NES in HBc ARD. This putative NES is leptomycin B resistant. iv We demonstrated by co-immunoprecipitation that HBc ARD can physically interact with a cellular factor TAP/NXF1 (Tip-associated protein/nuclear export factor-1, which is known to be important for nuclear export of mRNA and proteins. Treatment with a TAP-specific siRNA strikingly shifted cytoplasmic HBc to nucleus, and led to a near 7-fold reduction of viral replication, and a near 10-fold reduction in HBsAg secretion. v HBc of mutant ARD-II+IV was accumulated predominantly in the nucleus in a mouse model by hydrodynamic delivery. In addition to the revised map of NLS, our results suggest that HBc could shuttle rapidly between nucleus and cytoplasm via a novel

  5. Nuclear export controls

    International Nuclear Information System (INIS)

    Thorne, C.E.

    1999-01-01

    One approach to describing the multilateral nuclear export controls is to do it according to time. This led to an interesting discovery, i.e. multilateral export controls have been defined by four distinct periods, the forst two of abut five years each, the second two about twice as long. These time periods have another interesting property. The two suppliers groups, which we will discuss in detail, have alternated in dominance over nearly thirty years. After describing the historical developments, the status of the present situation in multilateral nuclear export controls is examined, with the strengths and weaknesses. The future of multilateral nuclear export controls and possible ways that might be taken are considered

  6. ALS Associated Mutations in Matrin 3 Alter Protein-Protein Interactions and Impede mRNA Nuclear Export.

    Science.gov (United States)

    Boehringer, Ashley; Garcia-Mansfield, Krystine; Singh, Gurkaran; Bakkar, Nadine; Pirrotte, Patrick; Bowser, Robert

    2017-11-06

    Mutations in Matrin 3 have recently been linked to ALS, though the mechanism that induces disease in these patients is unknown. To define the protein interactome of wild-type and ALS-linked MATR3 mutations, we performed immunoprecipitation followed by mass spectrometry using NSC-34 cells expressing human wild-type or mutant Matrin 3. Gene ontology analysis identified a novel role for Matrin 3 in mRNA transport centered on proteins in the TRanscription and EXport (TREX) complex, known to function in mRNA biogenesis and nuclear export. ALS-linked mutations in Matrin 3 led to its re-distribution within the nucleus, decreased co-localization with endogenous Matrin 3 and increased co-localization with specific TREX components. Expression of disease-causing Matrin 3 mutations led to nuclear mRNA export defects of both global mRNA and more specifically the mRNA of TDP-43 and FUS. Our findings identify a potential pathogenic mechanism attributable to MATR3 mutations and further link cellular transport defects to ALS.

  7. The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation.

    Science.gov (United States)

    Li, Ping; Stumpf, Maria; Müller, Rolf; Eichinger, Ludwig; Glöckner, Gernot; Noegel, Angelika A

    2017-08-22

    SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.

  8. Canada's nuclear export policy

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, R W; Wonder, E F [Carleton Univ., Ottawa, Ontario (Canada)

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology.

  9. Canada's nuclear export policy

    International Nuclear Information System (INIS)

    Morrison, R.W.; Wonder, E.F.

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology. (O.T.)

  10. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  11. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available Transport of messenger RNA (mRNA from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex.

  12. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  13. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

    Science.gov (United States)

    Alefantis, Timothy; Barmak, Kate; Harhaj, Edward W; Grant, Christian; Wigdahl, Brian

    2003-06-13

    Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

  14. Nuclear exporters cartel

    International Nuclear Information System (INIS)

    Mandelbaum, M.

    1977-01-01

    Events that have transpired in the past few years that have caused renewed concern about the spread of nuclear weapons are reviewed. Many proposals have been made recently for keeping the bomb from spreading. The author feels that the most novel and intriguing of them is the one advanced by Senator Abraham Ribicoff and Steven J. Baker; in their proposal, the world market for nuclear reactors would be divided into precisely defined shares among the industrial nations that now manufacture them for export; each exporter would be guaranteed a certain number of sales annually; and each would pledge not to sell uranium enrichment or plutonium reprocessing technology, as Germany did to Brazil. This might not halt proliferation, but it would give the world a few more years to find a solution

  15. Russian nuclear industry exports

    International Nuclear Information System (INIS)

    Gorbatchev, A.

    2016-01-01

    Rosatom is the world leader for the export of nuclear technologies. 34 reactors of Russian technology are being built or planned worldwide. Most reactors proposed by Rosatom are third generation VVER-1200 units with an electric power output of 1200 MWe. Although the nuclear island is always built by Rosatom, the remain of the plant can be subcontracted to other enterprises and European companies are sought because they would bring a european quality touch to Russian works. One of the main assets of Rosatom is to propose an integrated offer from supplying nuclear fuel to managing nuclear waste via the turnkey building of nuclear power plants. Another important asset is the financial assistance of the Russian state through state credit or the support from Russian national banks that appears to be a decisive advantage in the international competition to win markets. We have to temper the Russian export perspectives by noting that most projects are set in countries that are prone to instabilities and that the economic crisis affecting Russia has a negative impact on its financial means. (A.C.)

  16. Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery

    International Nuclear Information System (INIS)

    Audsley, Michelle D.; Jans, David A.; Moseley, Gregory W.

    2016-01-01

    Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion. - Highlights: • A new model for Nipah virus W protein nucleocytoplasmic trafficking is proposed. • Nipah W protein is shown to undergo active nuclear export via exportin-1. • Nipah W nuclear import is mediated by multiple nuclear localisation signals.

  17. An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway.

    Directory of Open Access Journals (Sweden)

    Mariana Serpeloni

    Full Text Available In eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II, but not RNA polymerase I (RNA pol I or Spliced Leader (SL transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and

  18. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function

    Directory of Open Access Journals (Sweden)

    St-Laurent Georges

    2006-11-01

    Full Text Available Abstract Background The HIV Rev protein is known to facilitate export of incompletely spliced and unspliced viral transcripts to the cytoplasm, a necessary step in virus life cycle. The Rev-mediated nucleo-cytoplasmic transport of nascent viral transcripts, dependents on interaction of Rev with the RRE RNA structural element present in the target RNAs. The C-terminal variant of dsRNA-binding nuclear protein 90 (NF90ctv has been shown to markedly attenuate viral replication in stably transduced HIV-1 target cell line. Here we examined a mechanism of interference of viral life cycle involving Rev-NF90ctv interaction. Results Since Rev:RRE complex formations depend on protein:RNA and protein:protein interactions, we investigated whether the expression of NF90ctv might interfere with Rev-mediated export of RRE-containing transcripts. When HeLa cells expressed both NF90ctv and Rev protein, we observed that NF90ctv inhibited the Rev-mediated RNA transport. In particular, three regions of NF90ctv protein are involved in blocking Rev function. Moreover, interaction of NF90ctv with the RRE RNA resulted in the expression of a reporter protein coding sequences linked to the RRE structure. Moreover, Rev influenced the subcellular localization of NF90ctv, and this process is leptomycin B sensitive. Conclusion The dsRNA binding protein, NF90ctv competes with HIV Rev function at two levels, by competitive protein:protein interaction involving Rev binding to specific domains of NF90ctv, as well as by its binding to the RRE-RNA structure. Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv.

  19. Analysis of nuclear export using photoactivatable GFP fusion proteins and interspecies heterokaryons.

    Science.gov (United States)

    Nakrieko, Kerry-Ann; Ivanova, Iordanka A; Dagnino, Lina

    2010-01-01

    In this chapter, we review protocols for the analysis of nucleocytoplasmic shuttling of transcription factors and nuclear proteins, using two different approaches. The first involves the use of photoactivatable forms of the protein of interest by fusion to photoactivatable green fluorescent protein to follow its movement out of the nucleus by live-cell confocal microscopy. This methodology allows for the kinetic characterization of protein movements as well as measurement of steady-state levels. In a second procedure to assess the ability of a nuclear protein to move into and out of the nucleus, we describe the use of interspecies heterokaryon assays, which provide a measurement of steady-state distribution. These technologies are directly applicable to the analysis of nucleocytoplasmic movements not only of transcription factors, but also other nuclear proteins.

  20. eEF1A Mediates the Nuclear Export of SNAG-Containing Proteins via the Exportin5-Aminoacyl-tRNA Complex

    Directory of Open Access Journals (Sweden)

    José Manuel Mingot

    2013-11-01

    Full Text Available Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

  1. The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export*

    Science.gov (United States)

    Port, Sarah A.; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H.

    2016-01-01

    Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A)+ RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. PMID:27613868

  2. The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export.

    Science.gov (United States)

    Port, Sarah A; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H

    2016-10-28

    Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A) + RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A) + RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Interaction of HTLV-1 Tax protein with the calreticulin: Implications for Tax nuclear export and secretion

    OpenAIRE

    Alefantis, Timothy; Flaig, Katherine E.; Wigdahl, Brian; Jain, Pooja

    2007-01-01

    Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to t...

  4. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1

    International Nuclear Information System (INIS)

    Zheng Chunfu; Brownlie, Robert; Babiuk, Lorne A.; Hurk, Sylvia van Drunen Littel-van den

    2004-01-01

    Bovine herpesvirus-1 (BHV-1) VP8 is found in the nucleus immediately after infection. Transient expression of VP8 fused to yellow fluorescent protein (YFP) in COS-7 cells confirmed the nuclear localization of VP8 in the absence of other viral proteins. VP8 has four putative nuclear localization signals (NLS). Deletion of pat4 ( 51 RRPR 54 ) or pat7 ( 48 PRVRRPR 54 ) NLS2 abrogated nuclear accumulation, whereas deletion of 48 PRV 50 did not, so pat4 NLS2 is critical for nuclear localization of VP8. Furthermore, NLS1 ( 11 RRPRR 15 ), pat4 NLS2, and pat7 NLS2 were all capable of transporting the majority of YFP to the nucleus. Finally, a 12-amino-acid peptide with the sequence RRPRRPRVRRPR directed all of YFP into the nucleus, suggesting that reiteration of the RRPR motif makes the nuclear localization more efficient. Heterokaryon assays demonstrated that VP8 is also capable of shuttling between the nucleus and cytoplasm of the cell. Deletion mutant analysis revealed that this property is attributed to a leucine-rich nuclear export sequence (NES) consisting of amino acids 485 LSAYLTLFVAL 495 . This leucine-rich NES caused transport of YFP to the cytoplasm. These results demonstrate that VP8 shuttles between the nucleus and cytoplasm

  5. RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton.

    Science.gov (United States)

    Mamon, L A; Ginanova, V R; Kliver, S F; Yakimova, A O; Atsapkina, A A; Golubkova, E V

    2017-04-01

    The mutual relationship between mRNA and the cytoskeleton can be seen from two points of view. On the one hand, the cytoskeleton is necessary for mRNA trafficking and anchoring to subcellular domains. On the other hand, cytoskeletal growth and rearrangement require the translation of mRNAs that are connected to the cytoskeleton. β-actin mRNA localization may influence dynamic changes in the actin cytoskeleton. In the cytoplasm, long-lived mRNAs exist in the form of RNP (ribonucleoprotein) complexes, where they interact with RNA-binding proteins, including NXF (Nuclear eXport Factor). Dm NXF1 is an evolutionarily conserved protein in Drosophila melanogaster that has orthologs in different animals. The universal function of nxf1 genes is the nuclear export of different mRNAs in various organisms. In this mini-review, we briefly discuss the evidence demonstrating that Dm NXF1 fulfils not only universal but also specialized cytoplasmic functions. This protein is detected not only in the nucleus but also in the cytoplasm. It is a component of neuronal granules. Dm NXF1 marks nuclear division spindles during early embryogenesis and the dense body on one side of the elongated spermatid nuclei. The characteristic features of sbr mutants (sbr 10 and sbr 5 ) are impairment of chromosome segregation and spindle formation anomalies during female meiosis. sbr 12 mutant sterile males with immobile spermatozoa exhibit disturbances in the axoneme, mitochondrial derivatives and cytokinesis. These data allow us to propose that the Dm NXF1 proteins transport certain mRNAs in neurites and interact with localized mRNAs that are necessary for dynamic changes of the cytoskeleton. © 2017 Wiley Periodicals, Inc.

  6. Regulation of RNA-binding proteins affinity to export receptors enables the nuclear basket proteins to distinguish and retain aberrant mRNAs.

    Science.gov (United States)

    Soheilypour, M; Mofrad, M R K

    2016-11-02

    Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs. Our results show that the affinity between Tpr and RBPs is optimized to maximize the retention of aberrant mRNAs. In addition, we demonstrate how the length of mRNA affects the QC process. Since longer mRNAs spend more time in the nuclear basket to form a compact conformation and initiate their export, nuclear basket proteins could more easily capture and retain them inside the nucleus.

  7. Export markets for nuclear technology

    International Nuclear Information System (INIS)

    Huettl, A.J.

    1985-01-01

    By late 1984, nuclear power plants were in operation or under construction in 32 countries of the globe. An additional six countries had concrete plans for building nuclear power plants. Of these 38 countries, ten have shown that they posses the necessary know-how and the technical facilities to plan and build nuclear power plants practically on their own. Seven of these ten countries have already acted as exporters of nuclear power plants, albeit with very different degrees of market penetration. In addition, there have been a number of countries for quite some time whose industries have managed to manufacture many important nuclear power plant components. Their high level of technical development and the problems frequently encountered in export financing have made them very attractive partners of the true exporters of nuclear power plants. For the future, it must be expected that some of the countries which have so far limited their efforts to the construction of nuclear power plants at home will also develop into exporters of nuclear technology. The report contains a survey of the range of nuclear products available, a list of reactor vendors, reactor lines, and data on the economics of electricity generation in nuclear plants. It then goes on to offer detailed descriptions of the market and the demand situation. Interesting chapters are devoted to the selection criteria applied by importing countries, to financing problems, and to the influences exerted by the political environment. A realistic forecast is attempted in order to make a quantitative analysis of possible export contracts up until the year 2000. (orig.) [de

  8. Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery.

    Science.gov (United States)

    Yang, Ching-Chun; Huang, Er-Yi; Li, Hung-Cheng; Su, Pei-Yi; Shih, Chiaho

    2014-01-01

    Hepatitis B virus (HBV) core protein (HBc) can shuttle between nucleus and cytoplasm. Cytoplasm-predominant HBc is clinically associated with severe liver inflammation. Previously, we found that HBc arginine-rich domain (ARD) can associate with a host factor NXF1 (TAP) by coimmunoprecipitation. It is well known that NXF1-p15 heterodimer can serve as a major export receptor of nuclear mRNA as a ribonucleoprotein complex (RNP). In the NXF1-p15 pathway, TREX (transcription/export) complex plays an important role in coupling nuclear pre-mRNA processing with mRNA export in mammalian cells. Here, we tested the hypothesis whether HBc and HBV specific RNA can be exported via the TREX and NXF1-p15 mediated pathway. We demonstrated here that HBc can physically and specifically associate with TREX components, and the NXF1-p15 export receptor by coimmunoprecipitation. Accumulation of HBc protein in the nucleus can be induced by the interference with TREX and NXF1-p15 mediated RNA export machinery. HBV transcripts encodes a non-spliced 3.5 kb pregenomic RNA (pgRNA) which can serve as a template for reverse transcription. Cytoplasmic HBV pgRNA appeared to be reduced by siRNA treatment specific for the NXF1-p15 complex by quantitative RT-qPCR and Northern blot analyses. This result suggests that the pgRNA was also exported via the NXF1-p15 machinery. We entertain the hypothesis that HBc protein can be exported as an RNP cargo via the mRNA export pathway by hijacking the TREX and NXF1-p15 complex. In our current and previous studies, HBc is not required for pgRNA accumulation in the cytoplasm. Furthermore, HBc ARD can mediate nuclear export of a chimeric protein containing HBc ARD in a pgRNA-independent manner. Taken together, it suggests that while both pgRNA and HBc protein exports are dependent on NXF1-p15, they are using the same export machinery in a manner independent of each other.

  9. Nuclear exports and international cooperation

    International Nuclear Information System (INIS)

    McCardle, J.J.

    1981-06-01

    Canada's nuclear export policy together with its non-proliferation and safeguards policy embrace both the country's desire to promote international cooperation in the peaceful uses of nuclear energy and its effort to minimize the risk of further proliferation of nuclear weapons. This policy reflects the belief that only if Canadian parliamentary and public opinion can be convinced that Canada's nuclear exports will not contribute to nuclear proliferation will the long-term health of the country's nuclear industry be assured. Canada requires a political commitment to non-proliferation from its nuclear partners, and looks to the IAEA to administer safeguards on nuclear material of Canadian origin to guarantee that commitment. Agreements reached with its nuclear partners are in accordance with provisions of the non-proliferation treaty and include a contingency provision for fall-back safeguards if the other state should withdraw from the NPT. Provision is made for mutual agreement on reprocessing and enrichment of nuclear material. Agreements have been reached with some twenty nuclear partners, and efforts are continuing to come to new international understanding on reprocessing, enrichment, and plutonium storage

  10. Nuclear export controls and nuclear safeguards

    International Nuclear Information System (INIS)

    Sevini, F.

    2013-01-01

    The export control of dual use goods has developed since the early seventies to counter nuclear proliferation. The paper provides an overview of dual-use export control issues also in relation with the Additional Protocol to the Comprehensive Safeguards Agreement, which requires States to provide declarations of the export of the controlled items listed in its Annex II, derived from the Nuclear Suppliers Group Trigger list. Recommendations for improvement are proposed. On the EU level, the paper summarises the framework set by the European Council Regulation 428/2009, requiring Member States to impose control on exports, brokering and transit of dual use goods. The Regulation includes the so-called 'EU dual-use control list' integrating the lists of dual-use items defined by the international regimes and requires also the control on intangible technology transfers as foreseen by U.N. Security Council Resolution 1540. ESARDA has recently launched a new sub-Working Group on export control, which raised large interest and may evolve to a full-fledged working group. Export control may provide an opportunity of technical collaboration between ESARDA and INMM. The paper is followed by the slides of the presentation. (author)

  11. RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs

    DEFF Research Database (Denmark)

    Wang, Jiexin; Rajbhandari, Prashant; Damianov, Andrey

    2017-01-01

    A highly orchestrated gene expression program establishes the properties that define mature adipocytes, but the contribution of posttranscriptional factors to the adipocyte phenotype is poorly understood. Here we have shown that the RNA-binding protein PSPC1, a component of the paraspeckle complex...

  12. Nuclear safeguards and export controls

    International Nuclear Information System (INIS)

    Mueller, H.

    1994-01-01

    Precisely from the perspective of the two most important nonnuclear weapons states, Japan and Germany, the safeguards and arms control agendas have not been finally dealt with. Because of their central position in the nonproliferation regime as nuclear suppliers and states with large nuclear energy industries, both countries are compelled to take a leading role in pursuing future reforms. In the dialogue with the nonaligned, this leadership position is helped by their nonnuclear status. In fact, Japan and Germany have some interests in common with the nonaligned states, such as the expansion of safeguards in the nuclear weapons states. To be sure, both Japan and Germany will pursue such interests with due regard to the interests of their friends and allies. For Japan, maintaining a close relationship with the United States is as important as shaping viable relations with China. Initiatives and controversies on nuclear policy must be weighed against this interest. By the same token, Germany must take into account the dense network of relations with its allies and with Russia, in addition to the German-French friendship. This will always set limits to Germany's readiness to confront the nuclear weapons states on nuclear issues. This, however, does not mean that both countries must shut up when the P 5 speak. The nuclear weapons register and the extension of the ''erga omnes'' rule in export controls, for example, should not be relegated to the dustbin of history, just because some friendly nuclear powers don't like these ideas. (orig.)

  13. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

    Science.gov (United States)

    Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

    2014-01-01

    Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

  14. Protein export through the bacterial flagellar type III export pathway.

    Science.gov (United States)

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. All rights reserved.

  15. Nuclear export of RNA: Different sizes, shapes and functions.

    Science.gov (United States)

    Williams, Tobias; Ngo, Linh H; Wickramasinghe, Vihandha O

    2018-03-01

    Export of protein-coding and non-coding RNA molecules from the nucleus to the cytoplasm is critical for gene expression. This necessitates the continuous transport of RNA species of different size, shape and function through nuclear pore complexes via export receptors and adaptor proteins. Here, we provide an overview of the major RNA export pathways in humans, highlighting the similarities and differences between each. Its importance is underscored by the growing appreciation that deregulation of RNA export pathways is associated with human diseases like cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  16. Exporting nuclear engineering and the government's viewpoint

    International Nuclear Information System (INIS)

    Schill, H.

    1986-01-01

    The reasons for the government's positive attitude to nuclear engineering exports are explained, especially with regard to them being a compensation of the decreasing domestic demand. The federal government considers such exports to be necessary and correct for economical and energy-political reasons. Their contribution reaches from accompanying measures to the provision of state guarantees of export financing activities. (UA) [de

  17. Analysis and prediction of leucine-rich nuclear export signals

    DEFF Research Database (Denmark)

    La Cour, T.; Kiemer, Lars; Mølgaard, Anne

    2004-01-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators...... this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden...

  18. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    Science.gov (United States)

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  19. Nuclear exportation and importation - the Brazilian situation

    International Nuclear Information System (INIS)

    Lavos Coimbra, G.

    1986-01-01

    The author proposes to set up a working group which should be responsible for the compilation of laws, procedures, and national policies for the nuclear importation and exportation in the supplying and receiving countries. Shared international views would simplify the flow of imports and exports between the countries. The author describes the different phases of exportation and importation of nuclear material are processed in her country, Brazil. (CW) [de

  20. The export of China nuclear power

    International Nuclear Information System (INIS)

    Zhang Jian

    2012-01-01

    The article first introduces the meaning of nuclear power export, and then analyses the advantages of China nuclear industry based on the status and development of this industry. At the same time. the collection of nuclear development for the next 30 years of several nations in south-east Asia, south Asia, Middle East, Africa and South America is compiled, which could be a valuable reference for foreseeing nuclear power export market. Finally, as the situation throughout the world is considered, some suggestions are made that what else could be done for future development and export. (author)

  1. Exporting nuclear engineering and the industry's viewpoint

    International Nuclear Information System (INIS)

    Barthelt, K.

    1986-01-01

    Nuclear energy offers all possibilities to reduce the energy problems in the world which arise with the world-wide increasing population and the energy demand connected with it. The Federal Republic of Germany lives on the exports of refined technical methods which also include nuclear engineering. The exports of nuclear engineering should lead to a technology transfer with guidance and training on an equal basis between the industrial and developing countries. The preconditions of exporting nuclear-technical systems are a well-functioning domestic market and a certain support by the government, especially with regard to giving guarantees for the special exports risks of these big projects. On the other hand, exports are also needed in order to be able to continue providing high-level technology for the domestic market. (UA) [de

  2. The NPT and nuclear export controls

    International Nuclear Information System (INIS)

    Berkhout, F.

    1992-01-01

    Controls on the export of nuclear materials and technology were originally imposed in wartime and under the United States Atomic Energy Act of 1946 to restrict the supply of uranium. But there was no international agreement until the mid 1960s; before that the United States, Canada, France and the Soviet Union imposed export controls on a national basis. The Non-Proliferation Treaty, especially Articles I-IV, set out the first world wide controls on the nuclear trade. These articles are explained in the context of the relevant Committees (the Zangger Committee, the Committee on the Assurance of Supply, the National Export Committee and the Coordinating Committee for Multilateral Export Control) and Guidelines (the Nuclear Suppliers Guidelines and the International Nuclear Fuel Cycle Evaluation). Recent developments which have a bearing on nuclear trade, such as the single European market, the emergence of new supplies and the break-up of the Soviet Union, are considered. (UK)

  3. A quasi-lentiviral green fluorescent protein reporter exhibits nuclear export features of late human immunodeficiency virus type 1 transcripts

    International Nuclear Information System (INIS)

    Graf, Marcus; Ludwig, Christine; Kehlenbeck, Sylvia; Jungert, Kerstin; Wagner, Ralf

    2006-01-01

    We have previously shown that Rev-dependent expression of HIV-1 Gag from CMV immediate early promoter critically depends on the AU-rich codon bias of the gag gene. Here, we demonstrate that adaptation of the green fluorescent protein (GFP) reporter gene to HIV codon bias is sufficient to turn this hivGFP RNA into a quasi-lentiviral message following the rules of late lentiviral gene expression. Accordingly, GFP expression was significantly decreased in transfected cells strictly correlating with reduced RNA levels. In the presence of the HIV 5' major splice donor, the hivGFP RNAs were stabilized in the nucleus and efficiently exported to the cytoplasm following fusion of the 3' Rev-responsive element (RRE) and coexpression of HIV-1 Rev. This Rev-dependent translocation was specifically inhibited by leptomycin B suggesting export via the CRM1-dependent pathway used by late lentiviral transcripts. In conclusion, this quasi-lentiviral reporter system may provide a new platform for developing sensitive Rev screening assays

  4. Nuclear export controls - Closing the gaps

    International Nuclear Information System (INIS)

    Schmidt, Fritz W.

    2005-01-01

    Concerns over a nuclear 'black market' have focused international attention on the effectiveness of nuclear export controls. IAEA Director General Mohamed ElBaradei has stated that the emergence of a multinational illicit network demonstrated the inadequacy of the present export control system, that international cooperation on export controls lay on informal arrangements that were not only not binding but also limited in membership, and that export control information was not systematically shared with the IAEA. This criticism, often heard on the political level, does not really do justice to the work of export control groups. The emergence of a multinational illicit network does not necessarily prove failures in export control systems. Criminal activities, by definition, try to circumvent existing rules and regulations, or they exploit the absence of such rules on State level. To fight such individual cases is not so much a task of regular export control systems, whose function lies primarily in establishing standards and procedures for export controls on State level, but rather the task for intelligence services and their international cooperation. The basis of the export control regime is the Nuclear Non-Proliferation Treaty (NPT). Export controls can - and do - play an important role in fostering this universality goal by demanding the implementation of internationally agreed security standards in recipient countries before export licenses are granted. Drawn from the deliberations in the NPT conferences, the current standards to be demanded as conditions of supply are the following: Safeguards, Physical Protection, National export control provisions. According to the NPT system, export controls require IAEA verification in the recipient country. In addition, export controls enable States to provide information to the IAEA on exports and imports as required by the Additional Protocol. The 2005 NPT Review Conference will be an opportunity to review developments

  5. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Science.gov (United States)

    Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

    2013-01-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

  6. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

    Science.gov (United States)

    Booth, David S; Cheng, Yifan; Frankel, Alan D

    2014-12-08

    The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

  7. Nuclear exports. Parliamentary control and confidentiality

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2015-01-01

    With its decision taken on 21. October 2014 (Az.: 2 BvE 5/11) the Federal Constitutional Court (BVerfG) decided during court proceedings between administrative bodies on the scope and limits of the parliamentary right of information. Even though the proceeding did not deal with nuclear exports but arm exports, foreign trade law, however, does not only designate an export licence obligation for military weapons but also for so called dual-use goods meaning goods, which can be used both for friendly as well as for military purposes. The export of these goods requires according to the so-called Dual-Use Regulation (EG) 428/2009 a licence. Annex I category 0 of the regulation (EG) 428/2009 lists a variety of nuclear materials, plants and equipment items for which this licence applies. In the same manner as arm exports, also exports of nuclear dual-use goods are being discussed in a special cabinet committee, the Federal Security Council (BSR), which shall coordinate cross-departmentally the German security and defence policy under consideration of economic interests and which categorises its results, according to the rules of procedure, as confidential. Also legally not regulated but common ''preliminary enquiries'' at the responsible Federal Ministry or rather Federal Office of Economics and Export Control by companies which plan an export and want to affirm the general approval for their export business prior to conclusion of contract take not only place for arm exports but also for nuclear dual-use goods. The decision by the Federal Constitutional Court can be applied to consultations about the authorisation of nuclear dual-use goods.

  8. How the Eximbank helps US nuclear exporters

    International Nuclear Information System (INIS)

    Moore, J.L. Jr.

    1981-01-01

    The way in which the Export-Import Bank operates in support of the United States nuclear industry noting particularly its flexibility in responding to changing needs and budget constraints is described. (author)

  9. Exporting apocalypse: CANDU reactors and nuclear proliferation

    International Nuclear Information System (INIS)

    McKay, Paul.

    The author believes that the peaceful use of nuclear technology leads inevitably to the production of nuclear weapons, and that CANDU reactors are being bought by countries that are likely to build bombs. He states that exports of reactors and nuclear materials cannot be defended and must be stopped

  10. Nuclear export policy of the Reagan Administration

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, J F; Donnelly, W H [Library of Congress, Washington, DC (USA)

    1983-06-01

    The Reagan Administration maintains the Carter Administration's objective of non-proliferation of nuclear weapons as being fundamental to US nuclear export policy. However, it sees the USA as having another important role to play in influencing the use of nuclear power and the trading of related goods and technologies in other countries. While the Administration believes its policies will prove beneficial to the USA, there is concern that trade considerations are being given priority over preventing the proliferation of nuclear weapons.

  11. Oil exporting countries need nuclear power

    International Nuclear Information System (INIS)

    Stauffer, T.R.

    1982-01-01

    The economic rationale for nuclear power in the oil exporting countries is analysed, with the collateral objective of defining the size of the potential market in terms of the exporting countries' economic opportunities and energy needs. The need for appropriate new institutions for licensing reactors, training personnel, and starting up plants follows directly from the size of the market and the economic incentives for the oil exporters to husband gas and oil. Gas and oil resources of the Middle Eastern countries are discussed, and future electricity needs estimated. (author)

  12. Challenges to nuclear export controls today

    International Nuclear Information System (INIS)

    Chatelus, R.; Sevini, F.; Janssens, W.; Michel, Q.

    2014-01-01

    Nuclear energy and nuclear proliferation programs are potentially inter-twinned, which is a point to be taken into account when analysing the development of civil nuclear energy, both domestically and as foreign investment. International agreements ensure that the adhering countries fulfil their obligations and do not abuse civil nuclear programs for the production of nuclear weapons. Uranium enrichment is the process currently most focused on in this respect by recent news and recent technological and commercial developments. But also the so-called reactor-based pathway, with extraction of plutonium from spent nuclear fuel by reprocessing remains in the spotlight of inspectors. Two of the main and complementary pillars on which the prevention of such diversion relies, are Strategic Export Control and International Safeguards. Strategic export control is a key barrier against nuclear proliferation. In many countries including the EU, it is set by a legal framework, envisaging implementation, enforcement and prosecution. The goods that can exported only with authorisations are those identified by the international export control regimes; primarily the Nuclear Suppliers Group in the case of nuclear items. It is complemented by nuclear safeguards measures, and especially in the past few years, by the IAEA State Level concept, which looks at the overall country's potential, including its industrial structure to derive conclusions on the absence of undeclared activities. However, the strict control of goods and knowledge is a moving target, since technological developments, globalisation and the intensifying exchange of information via the worldwide web offer increasing opportunities to proliferators to acquire sensitive items and competencies, and create bigger challenges to enforcement, calling for new responses. Research and development programmes must be directed towards supporting the adaptation of current proliferation containment systems to these new

  13. Inhibiting cancer cell hallmark features through nuclear export inhibition.

    Science.gov (United States)

    Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

    2016-01-01

    Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

  14. Notice to exporters on products prohibited from export (nuclear material, equipment and large nuclear units)

    International Nuclear Information System (INIS)

    1988-01-01

    In order to ensure that the policy to avoid the proliferation of nuclear weapons is complied with, the French Administration applies stricter controls over the export of certain sensitive products, materials and equipment. To this effect, lists of such products, materials and equipment are published in the form of Notices to exporters and periodically revised. This Notice repeals and replaces the previous Notice published in the Official Gazette of 21 January 1986. Annex I contains the list of materials whose export is subject to nuclear non-proliferation controls. Annex II lists the equipment whose export is subject to the same controls. Annex III includes the list of large nuclear units for which an application for prior approval of export must be submitted to the Administrations concerned. (NEA) [fr

  15. New U.S. nuclear export legislation

    International Nuclear Information System (INIS)

    Patermann, C.

    1978-01-01

    The new 1978 Export Control Act of the United States of America introduces a comprehensive arrangement of the criteria, responsibilities and procedures associated with nuclear exports, especially under the nonproliferation aspect. After a detailed analysis of the multitude of provisions it must be feared that, merely as a result of the high degree of formalization, bureaucratization and politicalization of these procedures, the U.S. can henceforth no longer be regarded as a reliable source of nuclear materials and facilities. An aspect received abroad with particular anguish is the fact that this unilateral aggravation of export controls was initiated after the start of the two-year INFCE program for international fuel cycle evaluation and that the new legislation forces the American government to renegotiate existing agreements on cooperation with the receiver countries under the threat of a delivery stop. (orig.) [de

  16. Nuclear technology and the export control laws

    International Nuclear Information System (INIS)

    Munroe, J.L.; Pankratz, M.C.; Hogsett, V.H.; Lundy, A.S.

    1988-01-01

    Three basic US laws regulate the export of commodities, services, and technical data. People working in nuclear fields need to know of these laws and their impact on professional endeavors. Export of technical data means the communication of any information by oral, written, or any other means to foreign nationals within or outside the US. The medium for the communication may be a model, blueprint, sketch, or any other device that can convey information. If the data relates to items on one of the control lists, a license must be sought from the appropriated federal agency. The Militarily Critical Technologies List (MCTL), though not itself a control list, plays a major role in determining what technical data will require a validated license. The US Department of Energy (DOE), through Technical Working Gorup (TWG) 11, is responsible for the Nuclear Technology chapter of the MCTL. TWG 11 also prepares the Nuclear Technology Reference Book (NTRB), a classified guide to sensitive nuclear technology

  17. Know-how and nuclear exports

    International Nuclear Information System (INIS)

    Luxo, A.

    1978-01-01

    The concrete content of nuclear know-how is defined, and the present position as to the exchange of know-how is discussed. The new forms which may be taken by this know-how are considered and the results which may be expected from a know-how transfer (both for the exporting and the importing countries) are related [fr

  18. Exportin-5 mediates nuclear export of SRP RNA in vertebrates.

    Science.gov (United States)

    Takeiwa, Toshihiko; Taniguchi, Ichiro; Ohno, Mutsuhito

    2015-04-01

    The signal recognition particle is a ribonucleoprotein complex that is essential for the translocation of nascent proteins into the endoplasmic reticulum. It has been shown that the RNA component (SRP RNA) is exported from the nucleus by CRM1 in the budding yeast. However, how SRP RNA is exported in higher species has been elusive. Here, we show that SRP RNA does not use the CRM1 pathway in Xenopus oocytes. Instead, SRP RNA uses the same export pathway as pre-miRNA and tRNA as showed by cross-competition experiments. Consistently, the recombinant Exportin-5 protein specifically stimulated export of SRP RNA as well as of pre-miRNA and tRNA, whereas an antibody raised against Exportin-5 specifically inhibited export of the same RNA species. Moreover, biotinylated SRP RNA can pull down Exportin-5 but not CRM1 from HeLa cell nuclear extracts in a RanGTP-dependent manner. These results, taken together, strongly suggest that the principal export receptor for SRP RNA in vertebrates is Exportin-5 unlike in the budding yeast. © 2015 The Authors. Genes to Cells published by Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  19. NPT, export controls and nuclear trade

    International Nuclear Information System (INIS)

    Pande, Savita

    1997-01-01

    Nuclear trade has by and large remained unhampered vis-a-vis both the NPT as well as export control regulations. The NPT rules are regarded as insufficient, the guidelines appear to contravene the spirit of cooperation in trade and development between suppliers and recipients and there is no agreement among leading suppliers themselves on what constitutes the proper conduct of trade. Export control regimes are more or less too informal to be able to be implemented. The supplier states have to invariably depend on national legislations which again vary from country to country. The only common formal basis on which action can be taken is, therefore, the NPT, its loopholes notwithstanding. The idea of transparency, and supplier-recipient dialogue continues to be a myth and will continue to be so long as these regimes remain discriminatory, so long as some nations are more powerful than others by virtue of retaining nuclear weapons and superiority in nuclear technology and trade

  20. German nuclear fuel exports and imports 1991

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The statistics compiled by the German Federal Office for Trade and Industry (Bundesamt fuer Wirtschaft) for the Federal Ministry for the Environment, Conservation of Nature, and Reactor Safety of imports and exports of nuclear fuels and source materials in 1991 show a major drop by 33.8% in imports and a pronounced rise by 191.5% in exports, compared to the levels in the previous year. Source material for the purposes of these statistics refers only to uranium concentrate. Quantitatively, the biggest import items are source materials, depleted uranium, and uranium enriched up to 3%. Exports of unirradiated material quantitatively comprise mainly depleted uranium, source material, and uranium enriched up to 10%. (orig.) [de

  1. Subcellular sites for bacterial protein export

    NARCIS (Netherlands)

    Campo, Nathalie; Tjalsma, Harold; Buist, Girbe; Stepniak, Dariusz; Meijer, Michel; Veenhuis, Marten; Westermann, Martin; Müller, Jörg P.; Bron, Sierd; Kok, Jan; Kuipers, Oscar P.; Jongbloed, Jan D.H.

    2004-01-01

    Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA-YEG pathway. In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the

  2. Subcellular sites for bacterial protein export.

    NARCIS (Netherlands)

    Campo, N.; Tjalsma, H.; Buist, G.; Stepniak, D.; Meijer, M.; Veenhuis, M.; Westermann, M.; Muller, J.P.; Bron, S.; Kok, J.; Kuipers, O.P.; Jongbloed, J.D.

    2004-01-01

    Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA-YEG pathway. In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the

  3. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

    Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  4. Hierarchical protein export mechanism of the bacterial flagellar type III protein export apparatus.

    Science.gov (United States)

    Minamino, Tohru

    2018-06-01

    The bacterial flagellum is supramolecular motility machinery consisting of the basal body, the hook and the filament. Flagellar proteins are translocated across the cytoplasmic membrane via a type III protein export apparatus, diffuse down the central channel of the growing structure and assemble at the distal end. Flagellar assembly begins with the basal body, followed by the hook and finally the filament. The completion of hook assembly is the most important morphological checkpoint of the sequential flagellar assembly process. When the hook reaches its mature length of about 55 nm in Salmonella enterica, the type III protein export apparatus switches export specificity from proteins required for the structure and assembly of the hook to those responsible for filament assembly, thereby terminating hook assembly and initiating filament assembly. Three flagellar proteins, namely FliK, FlhB and FlhA, are responsible for this substrate specificity switching. Upon completion of the switching event, interactions among FlhA, the cytoplasmic ATPase complex and flagellar type III export chaperones establish the assembly order of the filament at the hook tip. Here, we describe our current understanding of a hierarchical protein export mechanism used in flagellar type III protein export.

  5. Export and import provisions for nuclear materials and power plants

    International Nuclear Information System (INIS)

    Malsch, M.G.

    1976-01-01

    The present paper deals with 1) statutory requirements for export and import licensing of nuclear reactors and fuels; 2) regulations and procedures to issuance of exportlicenses; 3) environmental impact of export licensing; 4) licensing of reactor equipment; 5) recent restrictions on imports and exports of nuclear fuels. (RW) [de

  6. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

  7. Overview of nuclear export policies of major foreign supplier nations

    International Nuclear Information System (INIS)

    1977-01-01

    The United States faces increased competition from foreign nuclear suppliers, including West Germany, France, the United Kingdom, Canada, and possibly, in the near future, Japan. This general overview shows the differences and similarities in foreign nuclear supplier export requirements. It is based on summaries furnished by the Department of State covering the nuclear export policies and procedures of the major foreign supplier nations

  8. Nuclear export criteria and controls in the United States

    International Nuclear Information System (INIS)

    Shapar, H.K.

    1979-01-01

    The paper describes the export licensing procedure and the modifications made to it under the 1978 Nuclear Non-Proliferation Act (NNPA) to achieve greater control over exports of nuclear material and facilities. Export licences from the Nuclear Regulatory Commission are now required for certain items connected with nuclear plant construction and the procedure for obtaining the views of the Executive Branch have been formalised. The President is enabled to override the denial of an export licence by the NRC. Amongst the new criteria on the export licensing procedure added to the 1954 Atomic Energy Act, the NNPA provides that the IAEA Safeguards under the Non-Proliferation Treaty are applicable to exported nuclear material or facilities, together with adequate physical protection measures. (NEA) [fr

  9. Regulation of p53 tetramerization and nuclear export by ARC.

    Science.gov (United States)

    Foo, Roger S-Y; Nam, Young-Jae; Ostreicher, Marc Jason; Metzl, Mark D; Whelan, Russell S; Peng, Chang-Fu; Ashton, Anthony W; Fu, Weimin; Mani, Kartik; Chin, Suet-Feung; Provenzano, Elena; Ellis, Ian; Figg, Nichola; Pinder, Sarah; Bennett, Martin R; Caldas, Carlos; Kitsis, Richard N

    2007-12-26

    Inactivation of the transcription factor p53 is central to carcinogenesis. Yet only approximately one-half of cancers have p53 loss-of-function mutations. Here, we demonstrate a mechanism for p53 inactivation by apoptosis repressor with caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The direct binding in the nucleus of ARC to the p53 tetramerization domain inhibits p53 tetramerization. This exposes a nuclear export signal in p53, triggering Crm1-dependent relocation of p53 to the cytoplasm. Knockdown of endogenous ARC in breast cancer cells results in spontaneous tetramerization of endogenous p53, accumulation of p53 in the nucleus, and activation of endogenous p53 target genes. In primary human breast cancers with nuclear ARC, p53 is almost always WT. Conversely, nearly all breast cancers with mutant p53 lack nuclear ARC. We conclude that nuclear ARC is induced in cancer cells and negatively regulates p53.

  10. The politics of fading dreams: Britain and the nuclear export business

    International Nuclear Information System (INIS)

    Boardman, R.; Grieve, M.

    1983-01-01

    The subject is discussed as follows: introduction to a chapter focused on the politics of Britain's foreign nuclear trade; export goals and the nuclear programme (discussion of Magnox, AGR, SGHWR and PWR); the pursuit of exports; nuclear exports and proliferation (reprocessing; fast reactors; plutonium; INFCE); public opinion, nuclear power and exports (interest groups); conclusions (Britain's nuclear exports and non-proliferation). (U.K.)

  11. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

    Science.gov (United States)

    Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

    2014-05-01

    In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

  12. Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export signal

    International Nuclear Information System (INIS)

    Sato, Hiroki; Masuda, Munemitsu; Miura, Ryuichi; Yoneda, Misako; Kai, Chieko

    2006-01-01

    Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the N proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway

  13. Political implications of US nuclear-export-policy development

    International Nuclear Information System (INIS)

    Johnson-Freese, J.S.

    1981-01-01

    There has been a great deal of international debate regarding how effective strict export controls on nuclear-energy supplies are toward a non-proliferation goal. With the Carter Administration, the debate was heightened by a new, more-vigorous US nuclear-export policy, much of which was codified by the Nuclear Non-Proliferation Act of 1978 (NNPA). Because of the US position in both the international non-proliferation regime and nuclear export market, the NNPA has had far-reaching consequences. The thesis of this paper is that a nuclear-export policy that fails to consider its short-term ramifications, as the NNPA has been accused of, will be self-defeating. If the US wants a viable worldwide nuclear non-proliferation policy, it must first direct its efforts toward building a domestic non-proliferation consensus, and then worldwide, rather than first setting a highly controversial policy and expecting other nations to fall into line. This work provides a comprehensive case study of US nuclear-export policy between the years 1976 to 1980 in support of the thesis. Further, the behavior and impact of the interest groups which seem to shape US nuclear-export policies is examined, and recommendations made regarding the role of groups in nuclear policy-making and implementation. Finally, recommendations are made regarding non-proliferation policy for the future, as it relates to nuclear exports

  14. Export financing of nuclear power plants - banks experience

    International Nuclear Information System (INIS)

    Loeber

    1977-01-01

    1) Dimension and volume of the export financing of a nuclear power plant: 1.1) export orders of a new dimension; 1.2) individual loans occurring in connection with the export of a nuclear power plant: a) financial loans for maturities falling due under the export portion of the project; b) financial loans for the settlement of down- and interim payments to be made in connection with the export portion of the project; c) financial loans for the payment of local costs; d) loans for the financing of fuel elements; 2) governmental export insurance; 3) export financing in the individual industrial countries: USA, France, Great Britain, Japan (EXIMBANK), FRG. (orig./HP) [de

  15. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    International Nuclear Information System (INIS)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-01-01

    Highlights: ► We found the putative nuclear export signal motif within human NANOG homeodomain. ► Leucine-rich residues are important for human NANOG homeodomain nuclear export. ► CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ( 125 MQELSNILNL 134 ) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-ΔNLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  16. The nuclear importation and exportation - The Brazilian situation

    International Nuclear Information System (INIS)

    Coimbra, G.L.

    1985-01-01

    The panorama of Brazilian economy emphasizing the measurements adopted by Brazilian government referring to importation and exportation policy is presented. The Brazilian Nuclear Program knows the nuclear trade gives good economic perspective. In the context of importation and exportation policy the laws concerned to nuclear trade transactions, taxes, national organizations responsible by the external trade policy and their attributions are presented. (M.C.K.) [pt

  17. NESmapper: accurate prediction of leucine-rich nuclear export signals using activity-based profiles.

    Directory of Open Access Journals (Sweden)

    Shunichi Kosugi

    2014-09-01

    Full Text Available The nuclear export of proteins is regulated largely through the exportin/CRM1 pathway, which involves the specific recognition of leucine-rich nuclear export signals (NESs in the cargo proteins, and modulates nuclear-cytoplasmic protein shuttling by antagonizing the nuclear import activity mediated by importins and the nuclear import signal (NLS. Although the prediction of NESs can help to define proteins that undergo regulated nuclear export, current methods of predicting NESs, including computational tools and consensus-sequence-based searches, have limited accuracy, especially in terms of their specificity. We found that each residue within an NES largely contributes independently and additively to the entire nuclear export activity. We created activity-based profiles of all classes of NESs with a comprehensive mutational analysis in mammalian cells. The profiles highlight a number of specific activity-affecting residues not only at the conserved hydrophobic positions but also in the linker and flanking regions. We then developed a computational tool, NESmapper, to predict NESs by using profiles that had been further optimized by training and combining the amino acid properties of the NES-flanking regions. This tool successfully reduced the considerable number of false positives, and the overall prediction accuracy was higher than that of other methods, including NESsential and Wregex. This profile-based prediction strategy is a reliable way to identify functional protein motifs. NESmapper is available at http://sourceforge.net/projects/nesmapper.

  18. A Study on Improvement of Export Control law's understanding for nuclear control items' exporters in Rep. of Korea

    International Nuclear Information System (INIS)

    Lim, Dong Hyuk; Choi, Sun Do; Yang, Seung Hyo

    2011-01-01

    According to export of UAE commercial reactor and JRTR(Jordan Research and Training Reactor) in 2009, Korea's international prestige has enhanced and it has been more important for researcher in charge of export control to understand and carry out duties on export control by obeying Nuclear Suppliers Group(NSG) Guidelines. Currently, the NSG tries to prevent the proliferation of nuclear weapons by harmonising export control systems of participating countries in relation to trade with nuclear commodities and nuclear-related dual-use materials, equipment, software and technology. In addition, through the implementation of two sets of Guidelines for nuclear exports and nuclear-related exports, the NSG aims to ensure that nuclear trade for peaceful purposes does not contribute to the proliferation of nuclear weapons or other nuclear explosive devices, and that international trade and cooperation in the nuclear field is not hindered unjustly in the process. However, there is still not a little confusion of export businesses owing to lack of understanding of nuclear items in Korea. Therefore, by correctly understanding export control systems, permits and licenses, ITT and persistingly communicating with export businesses, Researchers in charge of export control are able to eliminate confusion of production businesses regarding export and establish a export control culture

  19. Protein export in bacillus subtilis and escherichia coli

    NARCIS (Netherlands)

    Dijl, Jan Maarten van

    1990-01-01

    The export of heterologous proteins in Bacillus subtilis and Escherichia coli is often inefficient. Frequently observed problems are: 1) accumulation of the precursor form of the exported protein in the cytoplasm or in the membrane; 2), inefficient or incorrect processing of the precursor; 3),

  20. Legal problems concerning the export of nuclear power plants

    International Nuclear Information System (INIS)

    Pierer, Heinrich von.

    1977-01-01

    The legal problems raised by the export of nuclear power plants may be divided into three main categories: nuclear operator's liability for nuclear damage, the consequences for the supplier of the licensing requirements in the national laws of the buyer country and finally, the constraints of applying non-proliferation safeguards on export of nuclear equipment. As regards the third party liability regime in particular, the difficulties lie essentially in the insufficiency of the definition of the nuclear operator and the lack of harmonization in, or even the absence of national laws in this field. (NEA) [fr

  1. NLSdb-major update for database of nuclear localization signals and nuclear export signals.

    Science.gov (United States)

    Bernhofer, Michael; Goldberg, Tatyana; Wolf, Silvana; Ahmed, Mohamed; Zaugg, Julian; Boden, Mikael; Rost, Burkhard

    2018-01-04

    NLSdb is a database collecting nuclear export signals (NES) and nuclear localization signals (NLS) along with experimentally annotated nuclear and non-nuclear proteins. NES and NLS are short sequence motifs related to protein transport out of and into the nucleus. The updated NLSdb now contains 2253 NLS and introduces 398 NES. The potential sets of novel NES and NLS have been generated by a simple 'in silico mutagenesis' protocol. We started with motifs annotated by experiments. In step 1, we increased specificity such that no known non-nuclear protein matched the refined motif. In step 2, we increased the sensitivity trying to match several different families with a motif. We then iterated over steps 1 and 2. The final set of 2253 NLS motifs matched 35% of 8421 experimentally verified nuclear proteins (up from 21% for the previous version) and none of 18 278 non-nuclear proteins. We updated the web interface providing multiple options to search protein sequences for NES and NLS motifs, and to evaluate your own signal sequences. NLSdb can be accessed via Rostlab services at: https://rostlab.org/services/nlsdb/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Implementation of the Nuclear Export Control at KAERI

    International Nuclear Information System (INIS)

    Kim, Hyun-Jo; Lee, Byung-Doo; Lee, Sung-Ho

    2006-01-01

    Korea has joined multilateral export control regimes which include Wassenaar Arrangement(WA), Nuclear Suppliers Group(NSG), Missile Technology Control Regime(MTCR) and Australian Group(AG), and their guideline and control lists are reflected in domestic legislation. Also, Catch-all control entered into force on 1 January 2003 in Korea. The frequency of the exports of product as a result of R and D and cooperation with other countries has been increased at Korea Atomic Energy Research Institute (KAERI). Therefore, this report describes the implementation status of a nuclear export control at KAERI and points out the practical issues

  3. Information Interaction with IAEA on Nuclear Import and Export

    International Nuclear Information System (INIS)

    Osokina, A.; Snytnikov, A.

    2015-01-01

    This paper considers organizational aspects of nuclear import and export interaction between the Russian Federation and the Agency. Requirements of nuclear import and export in Russia, information submission procedure and forms are determined in RF Government Regulation No 973 from December 15th 2000. Particularly, according to these requirements Russian licenced organizations implementing nuclear import and export submit reports about appointed transfers to State Corporation 'Rosatom'. Regulations of State Corporation 'Rosatom' entrusted gathering and processing of reporting information and interaction with IAEA to FSUE 'SCC of Rosatom'. Regulations of reporting information interaction were developed by SCC and approved by State Corporation 'Rosatom'. Russian organizations send notifications to SCC using regulation electron or paper forms. Regulations determine information security measures in reporting process. Automated nuclear import and export accounting system developed by SCC provides data entering, keeping and processing, enables to choose and submit requested information in different formats. This system is integrated with State Nuclear Material Control and Accounting System. Also submitted information is regularly compared with customs declarations data to improve reliability and consistency of information. Generalized nuclear import and export data is using by Departments of State Corporation 'Rosatom' and transmitting to Federal Environmental, Industrial and Nuclear Supervision Service of Russia in agreed forms. Summary information about international nuclear transfers is sending to IAEA according to INFCIRC/207. Reporting information is coordinating. Messaging with IAEA is realized by email using enciphering program. (author)

  4. Safety and exportation of nuclear power stations

    International Nuclear Information System (INIS)

    Coudray, M.; Perrais, J.P.

    1976-01-01

    Safety problems arising from exportation are especially handled through the French exportation of PWR stations. Regulations differ widely from one country to another. However, very large use of American regulations is made and frequently there is a tendency to harden such or such clause in the quotation. Industry must be ready to give satisfaction to such demands of customers. Sometimes also, it is a mere duplication of French stations which is above all looked for. In that case, it is the problem of using French regulations abroad which arises. Desirable changes in examination proceedings are analyzed together with a French regulation effort aiming to make easier the promotion of their use abroad. Finally, safety may be a factor of success for exportation attempts. It is shown how useless some outbiddings may be, but also how, on the contrary, speeding up of research and development effort towards specific safety problems in case of exportation, is to be promoted [fr

  5. Study on the establishment of effective nuclear export system

    International Nuclear Information System (INIS)

    Kim, Byung Koo; So, Dong Sup; Baik, Dae Hyun; Kwack, Eun Ho; Shin, Jang Soo; Yoon, Wan Ki; Park, Wan Soo; Kim, Hyun Tae.

    1997-02-01

    To improve Korean nuclear export control system, the modification of the present export license procedure for the nuclear equipment and materials and the classification of control items and their related technologies are required. And it is also necessary to make a database of the original countries who have the right of prior consent. For the efficient export control of LWR items to DPRK, it is desirable to manage the export license scheme of nuclear reactor facility as a total package, and to prepare a control regime for the retransfer of nuclear reactor component such as reactor coolant pump and nuclear fuel whose technologies are not self-reliant. It is especially essential to prepare a systematic procedure for the supply of nuclear equipment and materials to DPRK in order to meet international guidelines of NSG and others through an accord on the nuclear cooperation between Republic of Korea (ROK) and DPRK. The principal elements to be included in the accord are the range of cooperation, the restriction within the peaceful uses, prior consent right in case of retransfer of important nuclear reactor components and of storage, transfer and changes of nuclear fuels, application of safeguards to the supplied Trigger list items, physical protection of nuclear material, requirement of the return of nuclear equipment and materials, and restriction right for the suspension or termination of the agreement. (author). 40 refs., 5 tabs., 8 figs

  6. French nuclear industry exportations: companies and organisations, achievements and projects

    International Nuclear Information System (INIS)

    Faudon, V.; Pailler, S.; Miniere, D.; Pouget-Abadie, X.; Journes, F.; Ouali, F.; Brochard, D.; Choho, T.; Lagarde, D.; Anglaret, P.; Kottman, G.; Mockly, D.; Ouzounian, G.; Cordier, P.Y.; Prenez, J.C.; Arpino, J.M.; Jaouen, C.; Jolly, B.

    2013-01-01

    This document gathers a series of short articles in which the following players: French Nuclear Safety Authority (ASN), Electricity of France (EdF), French Alternative Energies and Atomic Energy Commission (CEA), AREVA, ALSTOM, the Association of French Nuclear Industry Exporters (AIFEN), the National Radioactive Waste Management Agency (ANDRA) and the French Society of Nuclear Energy (SFEN) present their competencies in their respective fields and their strategies and commercial offers for exports. 2 articles are dedicated to the achievements of the French nuclear industry in China and another details the cooperation between SFEN and its foreign counterparts. Another article briefly presents the EPR and ATMEA reactors. (A.C.)

  7. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    International Nuclear Information System (INIS)

    Chen, Zhi; Liu, Shaoning; Sun, Wenbo; Chen, Lei; Yoo, Dongwan; Li, Feng; Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun; Zhou, Shun; Wu, Jiaqiang

    2016-01-01

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  8. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Liu, Shaoning [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province (China); Sun, Wenbo; Chen, Lei [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Yoo, Dongwan [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Feng [Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007 (United States); Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Zhou, Shun [College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109 (China); Wu, Jiaqiang, E-mail: wujiaqiang2000@sina.com [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); and others

    2016-12-15

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  9. Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP

    Science.gov (United States)

    Wickramasinghe, Vihandha O.; Andrews, Robert; Ellis, Peter; Langford, Cordelia; Gurdon, John B.; Stewart, Murray; Venkitaraman, Ashok R.; Laskey, Ronald A.

    2014-01-01

    The nuclear phase of the gene expression pathway culminates in the export of mature messenger RNAs (mRNAs) to the cytoplasm through nuclear pore complexes. GANP (germinal- centre associated nuclear protein) promotes the transfer of mRNAs bound to the transport factor NXF1 to nuclear pore complexes. Here, we demonstrate that GANP, subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression. PMID:24510098

  10. Export financing of nuclear power plants - banks experience

    International Nuclear Information System (INIS)

    Loeber

    1976-01-01

    Export financing of a nuclear power plant to be exported from Germany, is, in principle, provided by German commercial banks and KfW (Kreditanstalt fuer Wiederaufbau). As a rule, 50 per cent of the financing of maturities falling due under the export portion of the loan will be taken over by a banking syndicate of approximately 25 member banks, and the remaining 50 per cent would be provided by KfW. KfW and the commercial banks must grant their loans at the respective money market conditions. The banks' and KfW's loans will normally be disbursed pro rata delivery. (HP) [de

  11. Germany's imports and exports of nuclear fuels in 1981

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The statistics of imports and exports of nuclear fuels and basic materials which is set up by the Federal Authority for trade and industry for the Ministry of the Interior shows for 1981 (without taking the basic materials into account) a slight increase by 5% on the imports' side and also a slight increase by 10,5% on the exports' side. (orig./UA) [de

  12. Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells

    Science.gov (United States)

    Lombardi, Maria; Castoria, Gabriella; Migliaccio, Antimo; Barone, Maria Vittoria; Di Stasio, Rosina; Ciociola, Alessandra; Bottero, Daniela; Yamaguchi, Hiroshi; Appella, Ettore; Auricchio, Ferdinando

    2008-01-01

    In breast cancer cells, cytoplasmic localization of the estradiol receptor α (ERα) regulates estradiol-dependent S phase entry. We identified a nuclear export sequence (NES) in ERα and show that its export is dependent on both estradiol-mediated phosphatidylinositol-3-kinase (PI3K)/AKT activation and chromosome region maintenance 1 (CRM1). A Tat peptide containing the ERα NES disrupts ERα–CRM1 interaction and prevents nuclear export of ERα- and estradiol-induced DNA synthesis. NES-ERα mutants do not exit the nucleus and inhibit estradiol-induced S phase entry; ERα-dependent transcription is normal. ERα is associated with Forkhead proteins in the nucleus, and estradiol stimulates nuclear exit of both proteins. ERα knockdown or ERα NES mutations prevent ERα and Forkhead nuclear export. A mutant of forkhead in rhabdomyosarcoma (FKHR), which cannot be phosphorylated by estradiol-activated AKT, does not associate with ERα and is trapped in the nucleus, blocking S phase entry. In conclusion, estradiol-induced AKT-dependent phosphorylation of FKHR drives its association with ERα, thereby triggering complex export from the nucleus necessary for initiation of DNA synthesis and S phase entry. PMID:18644889

  13. Export of nuclear equipment and materials and the non-proliferation of nuclear weapons

    International Nuclear Information System (INIS)

    Courteix, Simone.

    1977-01-01

    The problem of the non-proliferation of nuclear weapons is one of great concern today despite the entry into force in the early '70s of the NPT. To master civilian nuclear technology implies the ability to develop nuclear explosive devices; therefore in recent years contacts have strengthened between countries exporting nuclear equipment, specially in the frame of the 'London Club' so as to ensure that their exports will not result in disseminating nuclear weapons. (NEA) [fr

  14. Characterization of the ptr5+ gene involved in nuclear mRNA export in fission yeast

    International Nuclear Information System (INIS)

    Watanabe, Nobuyoshi; Ikeda, Terumasa; Mizuki, Fumitaka; Tani, Tokio

    2012-01-01

    Highlights: ► We cloned the ptr5 + gene involved in nuclear mRNA export in fission yeast. ► The ptr5 + gene was found to encode nucleoporin 85 (Nup85). ► Seh1p and Mlo3p are multi-copy suppressors for the ptr5 mutation. ► Ptr5p/Nup85p functions in nuclear mRNA export through the mRNA export factor Rae1p. ► Ptr5p/Nup85p interacts genetically with pre-mRNA splicing factors. -- Abstract: To analyze the mechanisms of mRNA export from the nucleus to the cytoplasm, we have isolated eleven mutants, ptr [poly(A) + RNA transport] 1 to 11, which accumulate poly(A) + RNA in the nucleus at a nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr5–1 mutant shows dots- or a ring-like accumulation of poly(A) + RNA at the nuclear periphery after shifting to the nonpermissive temperature. We cloned the ptr5 + gene and found that it encodes a component of the nuclear pore complex (NPC), nucleoporin 85 (Nup85). The ptr5–1 mutant shows no defects in protein transport, suggesting the specific involvement of Ptr5p/Nup85p in nuclear mRNA export in S. pombe. We identified Seh1p, a nucleoporin interacting with Nup85p, an mRNA-binding protein Mlo3p, and Sac3p, a component of the TREX-2 complex involved in coupling of nuclear mRNA export with transcription, as multi-copy suppressors for the ptr5–1 mutation. In addition, we found that the ptr5–1 mutation is synthetically lethal with a mutation of the mRNA export factor Rae1p, and that the double mutant exaggerates defective nuclear mRNA export, suggesting that Ptr5p/Nup85p is involved in nuclear mRNA export through Rae1p. Interestingly, the ptr5–1 mutation also showed synthetic effects with several prp pre-mRNA splicing mutations, suggesting a functional linkage between the NPCs and the splicing apparatus in the yeast nucleus.

  15. An evaluation of Kazakhstan nuclear export control system

    International Nuclear Information System (INIS)

    Yeligbayeva, G.; Masenov, Ch.

    2002-01-01

    A system to control the export nuclear materials and technologies is a natural part of creating a self-sustaining government. The government of Kazakhstan has made a great deal of progress in building such a system. Control of export and import of nuclear materials and technologies and dual-use materials, related to nuclear activity, became one of the important part of mechanism of Non-Proliferation conditions realization in Kazakhstan. The system of export control has developed well over the 10 years. Kazakhstan is in the midst of a long process of building a functional export control system consistent with World standards. The state system of export control currently exists in Kazakhstan on the legislative base, and is based on efficient cooperation of the KAEC with a number of competent state bodies (Ministry of Economy, Ministry of Foreign Affairs, State Customs Committee) each of them has its own specific functions, duties and rights. The export is carried out using licenses, issued by the Ministry of Economy of the RK, according to applications of certain standard which are previously agreed with the KAEC under decision of the RK Government. The KAEC, acting on the base of export control principles and observance of international obligations on non-proliferation matter, makes decisions, only after thorough evaluation of ways of export and reliability of an end-user of the commodity, to agree the application for a license. The most fully developed aspect is the licensing process. General politics of export regulation in Kazakhstan are based on normative acts and rules, which are wholly appropriate (complementary) to the managing principles of nuclear export. There exists a full legal basis for the licensing system. But the process is going, some provisions is changing: in 2000 Kazakhstan corrected the export control law and approved the national control list very similar with EU control list, in 2002 the rules of the process of licensing the export and import

  16. Panel on nuclear export and proliferation

    International Nuclear Information System (INIS)

    Kimel, W.R.

    1977-01-01

    Summaries of six panelists' remarks make the following points: one cannot suppress nuclear weapons by suppressing nuclear power; a proliferated world would be extremely dangerous; US supports IAEA safeguards; plutonium shouldn't be recycled in power reactors; and the problem of nonproliferation is a social and institutional problem, not a technological one. Viewographs showing the semantics of proliferation, ways to get nuclear weapons materials, etc. are included

  17. Evaluating Russian Dual-Use Nuclear Exports

    National Research Council Canada - National Science Library

    Bitterman, Blaine S

    2007-01-01

    ...; however, some of its actions contradict its rhetoric. Although Russia's violation of international agreements on nonproliferation is minimal, it is important to understand why Russia transfers nuclear technology...

  18. Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex

    Directory of Open Access Journals (Sweden)

    Steven J. Schnell

    2014-11-01

    Full Text Available The locations of transcription and translation of mRNA in eukaryotic cells are spatially separated by the nuclear envelope (NE. Plenty of nuclear pore complexes (NPCs embedded in the NE function as the major gateway for the export of transcribed mRNAs from the nucleus to the cytoplasm. Whereas the NPC, perhaps one of the largest protein complexes, provides a relatively large channel for macromolecules to selectively pass through it in inherently three-dimensional (3D movements, this channel is nonetheless below the diffraction limit of conventional light microscopy. A full understanding of the mRNA export mechanism urgently requires real-time mapping of the 3D dynamics of mRNA in the NPC of live cells with innovative imaging techniques breaking the diffraction limit of conventional light microscopy. Recently, super-resolution fluorescence microscopy and single-particle tracking (SPT techniques have been applied to the study of nuclear export of mRNA in live cells. In this review, we emphasize the necessity of 3D mapping techniques in the study of mRNA export, briefly summarize the feasibility of current 3D imaging approaches, and highlight the new features of mRNA nuclear export elucidated with a newly developed 3D imaging approach combining SPT-based super-resolution imaging and 2D-to-3D deconvolution algorithms.

  19. Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export.

    Science.gov (United States)

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun; Hopper, Anita K

    2017-11-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67-Mtr2 (TAP-p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67-Mtr2 can substitute for Los1 in los1 Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67-Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. © 2017 Chatterjee et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Introduction to Technology Export License of Nuclear Facility

    International Nuclear Information System (INIS)

    Seo, Hana; Lee, Chansuh; Shin, Donghoon

    2014-01-01

    In this regime, the Nuclear Safety and Security Commission (NSSC) has authority on final decision making. And the Korea Institute of Nuclear nonproliferation and Control (KINAC) has missions to review the classification and export licensing technically. In principle, classification and export licensing are applied and reviewed individually. However, the number of application for classification and licensing has increased geometrically in the last three years. This is largely a due to the contract that the Republic of Korea (ROK) has finalized to build the UAE Barakah Nuclear Power Plant (BNPP) and Jordan Research and Training Reactor (JRTR). This circumstance brought an administrative burden for the government and related institutes as well as stakeholders. This article introduces the law related to the 'Technology Export License of Nuclear Facility' which was developed and legislated to improve the efficiency and effectiveness of commodities classification and export licensing. This system could significantly reduce the licensing burden for transferring the technologies. However, the classification and license on this system are still requested when transferring the goods. Therefore, KINAC will continue to figure out the needs for the stakeholders and keep searching for solutions to problems inherent in the industry

  1. Introduction to Technology Export License of Nuclear Facility

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hana; Lee, Chansuh; Shin, Donghoon [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2014-05-15

    In this regime, the Nuclear Safety and Security Commission (NSSC) has authority on final decision making. And the Korea Institute of Nuclear nonproliferation and Control (KINAC) has missions to review the classification and export licensing technically. In principle, classification and export licensing are applied and reviewed individually. However, the number of application for classification and licensing has increased geometrically in the last three years. This is largely a due to the contract that the Republic of Korea (ROK) has finalized to build the UAE Barakah Nuclear Power Plant (BNPP) and Jordan Research and Training Reactor (JRTR). This circumstance brought an administrative burden for the government and related institutes as well as stakeholders. This article introduces the law related to the 'Technology Export License of Nuclear Facility' which was developed and legislated to improve the efficiency and effectiveness of commodities classification and export licensing. This system could significantly reduce the licensing burden for transferring the technologies. However, the classification and license on this system are still requested when transferring the goods. Therefore, KINAC will continue to figure out the needs for the stakeholders and keep searching for solutions to problems inherent in the industry.

  2. Nuclear export and armament. New threats and peace perspectives

    International Nuclear Information System (INIS)

    Kubbig, B.W.; Mueller, H.

    1993-02-01

    The authors give a condensed analysis of safety and politico-economic dimensions regarding the further proliferation of nuclear weapons and carrier systems with which nuclear blasting charges can be transported. From the content: - Proliferation and non-proliferation: technology, economy and (international) law in a political historic survey. - Missile defense: appropriate technological answer to the political proliferation problem? -export strategies: USA and FRG in comparison, interest and policy of the European Community. - Components for an extensive proliferation strategy. (orig./HP) [de

  3. The nuclear export policy of the Reagan administration

    International Nuclear Information System (INIS)

    Pilat, J.F.; Donnelly, W.H.

    1983-01-01

    tThe Reagan Administration maintains the Carter Administration's objective of non-proliferation of nuclear weapons as being fundamental to US nuclear export policy. However, it sees the USA as having another important role to play in influencing the use of nuclear power and the trading of related goods and technologies in other countries. While the Administration believes its policies will prove beneficial to the USA, there is concern that trade considerations are being given priority over preventing the proliferation of nuclear weapons. (author)

  4. US Nuclear Non-Proliferation Policy: impact on exports and nuclear industry could not be determined

    International Nuclear Information System (INIS)

    Staats, E.B.

    1980-01-01

    The Nuclear Non-Proliferation Act of 1978 established new measures to prevent the diversion to weapons use of peaceful nuclear exports. It also created a policy to confirm US reliability as a nuclear supplier. GAO did not identify any export sales lost as a result of the Act, but did find indications that nonprofileration policies can influence export sales. Based on avavailable data, GAO could not determine the impact of the Act on the competitiveness of US nuclear exports. However, US companies are at some disadvantage because importers perceive that implementation of the Act may result in delayed export licenses. The United States dominated the nuclear export market through the early 1970s. However, foreign competitors, some aided by US technology transfers, emerged to monopolize home markets and complete for third-country business. Further, the market has been depressed since 1974 and prospects for US nuclear power plant exports have dimmed greatly. However, US companies continue to view exports as important to sustain production capacity

  5. KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

    Science.gov (United States)

    Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

    2018-04-10

    Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Study on status of nuclear export/import implementation in KAERI

    International Nuclear Information System (INIS)

    Kim, H. J.; Lee, B. D.; Lee, S. H.; Park, H. J.; So, D. S.

    2004-01-01

    As Korea is the member of ZC(Zangger Committee) and NSG(Nuclear Suppliers Group), domestic legislation reflected their guideline of nuclear export. The paper investigate the status of implementation procedures of nuclear export and import in KAERI based on domestic and international law. In addition, the paper analyzes on problem of export/import implementation system and also extract the efficient implementation system of nuclear export and import

  7. Upgrading the safety assessment of exported nuclear power plants

    International Nuclear Information System (INIS)

    Rosen, M.

    1978-01-01

    An examination of the safety aspects of exported nuclear power plants demonstrates that additional and somewhat special considerations exist for these plants, and thus that some new approaches may be required to insure their safety. In view of the generally small regulatory staffs of importing countries, suggestions are given for measures which should be taken by the various organizations involved in the export and import of nuclear power facilities to raise the level of the very essential safety assessment. These include the upgrading of the 'export edition' of the traditionally supplied safety documentation by use of a Supplementary Information Report, written specifically for the needs of a smaller and/or less technically qualified staff, which highlights the differences that exist between the facility to be constructed and the supposedly similar reference plant of the supplier country; by improvement of supporting safety documentation to allow for adequate understanding of significant safety parameters; and by attention to the needs of smaller countries in the critical Operating Regulations (Technical Specifications for Operation). Consideration is also given to upgrading the regulatory effort and to the obligations of principal organizations involved with exported nuclear plants, including national and international, for insuring the importing countries' technical readiness and the adequacy of the regulatory effort. Special attention is directed towards the project contract as a means of implementing programmes to achieve these goals. (author)

  8. A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

    Science.gov (United States)

    Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

    2017-06-01

    The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  9. Nuclear Import and Export of the Thyroid Hormone Receptor.

    Science.gov (United States)

    Zhang, Jibo; Roggero, Vincent R; Allison, Lizabeth A

    2018-01-01

    The thyroid hormone receptors, TRα1 and TRβ1, are members of the nuclear receptor superfamily that forms one of the most abundant classes of transcription factors in multicellular organisms. Although primarily localized to the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. The fine balance between nuclear import and export of TRs has emerged as a critical control point for modulating thyroid hormone-responsive gene expression. Mutagenesis studies have defined two nuclear localization signal (NLS) motifs that direct nuclear import of TRα1: NLS-1 in the hinge domain and NLS-2 in the N-terminal A/B domain. Three nuclear export signal (NES) motifs reside in the ligand-binding domain. A combined approach of shRNA-mediated knockdown and coimmunoprecipitation assays revealed that nuclear entry of TRα1 is facilitated by importin 7, likely through interactions with NLS-2, and importin β1 and the adapter importin α1 interacting with both NLS-1 and NLS-2. Interestingly, TRβ1 lacks NLS-2 and nuclear import depends solely on the importin α1/β1 heterodimer. Heterokaryon and fluorescence recovery after photobleaching shuttling assays identified multiple exportins that play a role in nuclear export of TRα1, including CRM1 (exportin 1), and exportins 4, 5, and 7. Even single amino acid changes in TRs dramatically alter their intracellular distribution patterns. We conclude that mutations within NLS and NES motifs affect nuclear shuttling activity, and propose that TR mislocalization contributes to the development of some types of cancer and Resistance to Thyroid Hormone syndrome. © 2018 Elsevier Inc. All rights reserved.

  10. Nuclear Export Control Policy in Korea - Present and future

    International Nuclear Information System (INIS)

    Kim, Jongsook

    2008-01-01

    The International community has been facing with the continued challenges for possession and proliferation of WMD over the past years. In addition, it is known that the terrorist groups are interested in acquiring WMD. The black market of WMD related materials and technologies show also the one of seriousness of our challenges. A number of international treaties, agreements and initiatives to control the proliferation of weapons of N, B, C and their delivery system have been existed to deal with these challenges, but their missions are challenged greatly in recent a series of nuclear issues by Iran and North Korea. The paper reviews the current international export control status and Korea export control system and policy. It also addresses some agenda to be done as future export control policy in Korea

  11. Government experience in nuclear power plant export financing

    International Nuclear Information System (INIS)

    Kalbitz, K.

    1976-01-01

    Because the long-term funds at the disposal of the commercial banks were insufficient to make available the amounts required for the exportation of nuclear power plants, it was necessary to make available long-term funds of the mortgage banks. On account of the strict regulations governing the lending operations of such banks, it was, however, necessary to introduce a Federal guarantee which covers 100% of the contract value in each case. On balance, however, the Federal Government does not take over any additional risks, because recourse may be taken to the commercial banks, which are liable for all additional payments under the credit arrangement having arisen from the improvement of the guarantee in favour of the mortgage banks. This has resulted in a considerable improvement of the export financing system which, of course, is for benefit of other major export projects too. (HP) [de

  12. High-Resolution Imaging Reveals New Features of Nuclear Export of mRNA through the Nuclear Pore Complexes

    Directory of Open Access Journals (Sweden)

    Joseph M. Kelich

    2014-08-01

    Full Text Available The nuclear envelope (NE of eukaryotic cells provides a physical barrier for messenger RNA (mRNA and the associated proteins (mRNPs traveling from sites of transcription in the nucleus to locations of translation processing in the cytoplasm. Nuclear pore complexes (NPCs embedded in the NE serve as a dominant gateway for nuclear export of mRNA. However, the fundamental characterization of export dynamics of mRNPs through the NPC has been hindered by several technical limits. First, the size of NPC that is barely below the diffraction limit of conventional light microscopy requires a super-resolution microscopy imaging approach. Next, the fast transit of mRNPs through the NPC further demands a high temporal resolution by the imaging approach. Finally, the inherent three-dimensional (3D movements of mRNPs through the NPC demand the method to provide a 3D mapping of both transport kinetics and transport pathways of mRNPs. This review will highlight the recently developed super-resolution imaging techniques advanced from 1D to 3D for nuclear export of mRNPs and summarize the new features in the dynamic nuclear export process of mRNPs revealed from these technical advances.

  13. Nuclear exports and non-proliferation

    International Nuclear Information System (INIS)

    Courteix, Simone.

    1978-01-01

    Increased preoccupation in present times with the risk of proliferation of nuclear weapons is reflected in the multiplication of international agreements such as the Non-proliferation Treaty and in the strengthening of consultations between industrialised countries (London Club). After analysing the IAEA safeguards system under the Non-proliferation Treaty and its shortcomings both technically and otherwise, the author considers how this situation can be remedied in the light of the London Agreements and in view of the position of the main countries concerned. The annex to the book contains the texts of many international agreements and relevant national regulations as well as nuclear policy statements. It also includes a detailed bibliograaphy. (NEA) [fr

  14. SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export.

    Science.gov (United States)

    Müller-McNicoll, Michaela; Botti, Valentina; de Jesus Domingues, Antonio M; Brandl, Holger; Schwich, Oliver D; Steiner, Michaela C; Curk, Tomaz; Poser, Ina; Zarnack, Kathi; Neugebauer, Karla M

    2016-03-01

    Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends. © 2016 Müller-McNicoll et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Experience with the export of nuclear plants

    International Nuclear Information System (INIS)

    Huettl, A.

    1991-01-01

    Licensing and regulatory aspects represent an important issue during the definition and implementation phase of a nuclear power project. Strict adherence to the principles 'licensability in country of origin' and 'reference plant as built' may prove to be counterproductive on account of the differences in licensing infrastructure in vendor's and buyer's countries and of the difficulty in striking a balance between proven and up-to-date designs. In order to repeat good experience in safety, consistency of the applicable rules and regulations is important when performing the necessary adaptations to local requirements. The use of an internationally accepted body of rules such as NUSS as a yardstick for safety evaluation helps to identify special requirements in vendor's country, thus minimizing distortions in evaluation of competing bids. Benefitting from ongoing efforts to improve transparency and mutual understanding of the national safety approaches through bodies and missions like INSAG, WANO, OSART, a graded approach for implementing safety review during construction and operation is suggested, matching it to the scope of a national program of NPP construction. Together with efficient project control this will minimize the demands on resources - both human and financial - required for a successful launch of a nuclear power plant. (orig.)

  16. Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

    Science.gov (United States)

    Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

    2017-07-11

    Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

  17. Communication Received from Canada Regarding its New Nuclear Export Policy

    International Nuclear Information System (INIS)

    1977-01-01

    On 29 December 1976 the Director General received a letter dated 28 December from the Resident Representative of Canada to the Agency, informing him of a change in Canada's nuclear export policy and attaching a statement made in the Canadian House of Commons on this subject. In accordance with the request made by the Resident Representative of Canada the texts of his letter and of its attachment are reproduced below for the information of all Members.

  18. Import and export of small quantities of nuclear materials

    International Nuclear Information System (INIS)

    Grenier, M.

    1986-06-01

    Administrative procedures for import export of nuclear materials are specific for each country. In France regulations are reviewed for small quantities, lower threshold, in some cases, allows a simplified procedure, however thresholds are not the same in the different texts (and for one of them, concerning proliferation, is zero). It is obvious that regulations are necessary even for small quantities but national and international threshold should be harmonized [fr

  19. The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts

    DEFF Research Database (Denmark)

    Silla, Toomas; Karadoulama, Evdoxia; Mąkosa, Dawid

    2018-01-01

    , containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1......Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci...... but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export...

  20. The new US nuclear non-proliferation and export policy

    International Nuclear Information System (INIS)

    Welck, S. von.

    1981-01-01

    The future American nuclear non-proliferation and export policy will be determined chiefly by three elements: (1) Adherence to the former objective of nuclear non-proliferation. (2) A large and varied assortment of old and new tools for implementing this goal. (3) Much more differentiation in applying these tools in the light of the reliability, with respect to non-proliferation policy, of the respective partner. Consequently, it would make little sense for the new Administration to force upon allied industrialized countries, whose nuclear technologies are at the same level as that of the United States, restrictive rules on reprocessing and breeder technology. The new measures designed to curb proliferation are especially meant to destroy motivations that could cause states to own nuclear explosives. This also applies to the removal of economic motivations. (orig.) [de

  1. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2018-05-01

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

  3. O. Nuclear energy in a food exporting country

    International Nuclear Information System (INIS)

    1976-01-01

    This report attempts to estimate the affect on agricultural exports from New Zealand which might result from the operation of nuclear power. By far the most serious of these would result from an accidental release of radioactive material, and the likely affects of such releases are considered both in the first year after an accident and in the future. Previous assessments of this type have concentrated attention on property damage and on the health hazards which might result to consumers of contaminated food in the first year or two after a release. In this report the emphasis is on exported foods to which different criteria might apply, and some very approximate estimates are made of long-term implications. To a large extent these can be described only as speculations, but they have some value as a guide. No analgous report has been found in the open literature from other countries, and this particularly includes Denmark which has much in common with New Zealand in this regard. The possible effect of routine operation of nuclear power on food exports is also briefly considered

  4. Technical modifications and management innovations in exporting nuclear reactor projects

    International Nuclear Information System (INIS)

    Mao Xiaoming; Qin Xijiu; Ding Hu; Xue Zhaoqun; Wen Shengjun

    2009-01-01

    As a main channel for the foreign economic cooperation of China nuclear industry, China Zhongyuan Engineering Corporation (CZEC) has been constantly engaged in technical modifications and management innovations in its exporting nuclear reactor projects. In the implementation of heavy water research reactor contract in Algeria, CZEC had established a complete and adequate design standards system in compliance with the international standards, and made significant modifications to the reference reactor in the aspects of reactor power and reactor safety, solved quite some technical issues which-affected the reactor technical performance. The modifications and improvements enabled the technical parameters, safety features, reactor multipurpose application to attain to the advanced level in the world. In the 300 MWe PWR NPPs in Pakistan, safety features had been updated in line with upgrading regulatory requisites. The design philosophy and technology application demonstrated CZEC' s creation and innovation on basis of constant safety enhancement of nuclear power projects. Efforts had also been made by CZEC' s creation and innovation on basis of constant safety enhancement of nuclear power projects. Efforts had also been made by CZEC in promoting China made equipment items and components exportation. (authors)

  5. A Study on Improvement of Export Control law's understanding for nuclear control items' exporters in Rep. of Korea

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Dong Hyuk; Choi, Sun Do; Yang, Seung Hyo [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2011-10-15

    According to export of UAE commercial reactor and JRTR(Jordan Research and Training Reactor) in 2009, Korea's international prestige has enhanced and it has been more important for researcher in charge of export control to understand and carry out duties on export control by obeying Nuclear Suppliers Group(NSG) Guidelines. Currently, the NSG tries to prevent the proliferation of nuclear weapons by harmonising export control systems of participating countries in relation to trade with nuclear commodities and nuclear-related dual-use materials, equipment, software and technology. In addition, through the implementation of two sets of Guidelines for nuclear exports and nuclear-related exports, the NSG aims to ensure that nuclear trade for peaceful purposes does not contribute to the proliferation of nuclear weapons or other nuclear explosive devices, and that international trade and cooperation in the nuclear field is not hindered unjustly in the process. However, there is still not a little confusion of export businesses owing to lack of understanding of nuclear items in Korea. Therefore, by correctly understanding export control systems, permits and licenses, ITT and persistingly communicating with export businesses, Researchers in charge of export control are able to eliminate confusion of production businesses regarding export and establish a export control culture

  6. Functional analysis of the interaction of the human immunodeficiency virus type 1 Rev nuclear export signal with its cofactors

    International Nuclear Information System (INIS)

    Kiss, A.; Li, L.; Gettemeier, T.; Venkatesh, L.K.

    2003-01-01

    Human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export of viral RNAs involves the interaction of its leucine-rich nuclear export sequence (NES) with nuclear cofactors. In yeast two-hybrid screens of a human lymph node derived cDNA expression library, we identified the human nucleoporin Nup98 as a highly specific and potent interactor of the Rev NES. Using an extensive panel of nuclear export positive and negative mutants of the functionally homologous NESs of the HIV-1 Rev, human T cell leukemia virus type 1 (HTLV-1) Rex, and equine infectious anemia virus (EIAV) Rev proteins, physiologically significant interaction of hNup98 with the various NESs was demonstrated. Missense mutations in the yeast nuclear export factor Crm1p that abrogated Rev NES interaction with the XXFG repeat-containing nucleoporin, Rab/hRIP, had minimal effects on the interaction of GLFG repeat-containing hNup98. Functional analysis of Nup98 domains required for nuclear localization demonstrated that the entire ORF was required for efficient incorporation into the nuclear envelope. A putative nuclear localization signal was identified downstream of the GLFG repeat region. Whereas overexpression of both full-length Nup98 and the amino-terminal GLFG repeat region, but not the unique carboxy-terminal region, induced significant suppression of HIV unspliced RNA export, lower levels of exogenous Nup98 expression resulted in a relatively modest increase in unspliced RNA export. These results suggest a physiological role for hNup98 in modulating Rev-dependent RNA export during HIV infection

  7. Problems associated with the export of nuclear power plants

    International Nuclear Information System (INIS)

    1978-01-01

    Full text: Recent forecasts indicate that by the year 2000 there will be more than 1000 nuclear power plants operating in 50 countries and with several countries expecting to derive one-half or more of their electric generation from nuclear power plants At present only six countries are exporters of nuclear power systems, three more currently supply their own domestic markets, while the remainder are importers. It is expected that most of the importers will continue to depend to varying degrees on foreign supply, at least in the near future. If nuclear power is to offer an important benefit to the world, the achievement of this benefit will require co-operation between the supplying and receiving nations in overcoming problems which might inhibit the full development of this energy source. In addition to ensuring safety and reliability, special problem areas include financing, skilled manpower needs, adequate local industrial and engineering infrastructure, access to advanced technology, and an assured supply of nuclear fuel. The symposium had special emphasis on the problems facing many of the developing countries in the initial stages of nuclear power programmes, and was divided into three major topics nuclear safety, domestic contributions, and international aspects In the safety area, emphasis was given to the special considerations that may exist for countries that import nuclear plants. These special considerations can be due to some non-standard features of the exported reactor such as lower power ratings, dissimilar site characteristics that can effect the design, and the evolution and changes in design and safety requirements during construction. This can be complicated by differences in safety philosophy and codified standards of the various suppliers and unique construction problems in the less developed countries. Thus, the ability of the importing country to carry out the regulatory and safety function is obviously important. A number of presentations

  8. A common high standard for nuclear power plant exports: overview and analysis of the Nuclear Power Plant Exporters' Principles of Conduct

    International Nuclear Information System (INIS)

    Perkovich, George; Radzinsky, Brian

    2012-01-01

    At this time, there is no overarching global framework to regulate the development of the nuclear power industry. Laws concerning the export of nuclear technology vary across jurisdictions, and politically-binding arrangements such as the Nuclear Suppliers Group (NSG) help ensure that weapons-usable or dual-use technologies are not exported, but no single international regime or agreement manages the gamut of potential risks that may arise from the export of civilian nuclear power plants. Accordingly in 2008, the Carnegie Endowment for International Peace convened internationally-recognised experts in nuclear energy to begin a dialogue with nuclear power plant vendors about defining common criteria for the socially responsible export of nuclear power plants. The goal was to articulate a comprehensive set of principles and best practices that would raise the overall standard of practice for exports of nuclear power plants while enjoying widespread support and adherence. The outcome of this process is the Nuclear Power Plant Exporters' Principles of Conduct - an export-oriented code of conduct for nuclear power plant vendors. The Principles of Conduct help ensure that the participating companies will proceed with the sale of a new nuclear power plant only after a careful assessment of the legal, political, and technical contexts surrounding potential customers. It comprises six 'principles' that each address a major area of concern involved in the export of a nuclear power plant: safety, physical security, environmental protection and spent fuel management, systems of compensation for nuclear damage, non-proliferation and safeguards, and business ethics. The Principles of Conduct entail vendor responsibilities to apply specific standards or engage in certain practices before signing contracts and during the marketing and construction phases of a nuclear power plant export project. Conformity with the Principles of Conduct is voluntary and not-legally binding, but the

  9. Characterization of the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Nobuyoshi; Ikeda, Terumasa; Mizuki, Fumitaka [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer We cloned the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast. Black-Right-Pointing-Pointer The ptr5{sup +} gene was found to encode nucleoporin 85 (Nup85). Black-Right-Pointing-Pointer Seh1p and Mlo3p are multi-copy suppressors for the ptr5 mutation. Black-Right-Pointing-Pointer Ptr5p/Nup85p functions in nuclear mRNA export through the mRNA export factor Rae1p. Black-Right-Pointing-Pointer Ptr5p/Nup85p interacts genetically with pre-mRNA splicing factors. -- Abstract: To analyze the mechanisms of mRNA export from the nucleus to the cytoplasm, we have isolated eleven mutants, ptr [poly(A){sup +} RNA transport] 1 to 11, which accumulate poly(A){sup +} RNA in the nucleus at a nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr5-1 mutant shows dots- or a ring-like accumulation of poly(A){sup +} RNA at the nuclear periphery after shifting to the nonpermissive temperature. We cloned the ptr5{sup +} gene and found that it encodes a component of the nuclear pore complex (NPC), nucleoporin 85 (Nup85). The ptr5-1 mutant shows no defects in protein transport, suggesting the specific involvement of Ptr5p/Nup85p in nuclear mRNA export in S. pombe. We identified Seh1p, a nucleoporin interacting with Nup85p, an mRNA-binding protein Mlo3p, and Sac3p, a component of the TREX-2 complex involved in coupling of nuclear mRNA export with transcription, as multi-copy suppressors for the ptr5-1 mutation. In addition, we found that the ptr5-1 mutation is synthetically lethal with a mutation of the mRNA export factor Rae1p, and that the double mutant exaggerates defective nuclear mRNA export, suggesting that Ptr5p/Nup85p is involved in nuclear mRNA export through Rae1p. Interestingly, the ptr5-1 mutation also showed synthetic effects with several prp pre-mRNA splicing mutations, suggesting a functional linkage between the NPCs and the splicing apparatus in the yeast nucleus.

  10. IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

    Science.gov (United States)

    Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

    2017-10-09

    Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

  11. Deciphering mechanisms of drug sensitivity and resistance to Selective Inhibitor of Nuclear Export (SINE) compounds

    International Nuclear Information System (INIS)

    Crochiere, Marsha; Kashyap, Trinayan; Kalid, Ori; Shechter, Sharon; Klebanov, Boris; Senapedis, William; Saint-Martin, Jean-Richard; Landesman, Yosef

    2015-01-01

    Exportin 1 (XPO1) is a well-characterized nuclear export protein whose expression is up-regulated in many types of cancers and functions to transport key tumor suppressor proteins (TSPs) from the nucleus. Karyopharm Therapeutics has developed a series of small-molecule Selective Inhibitor of Nuclear Export (SINE) compounds, which have been shown to block XPO1 function both in vitro and in vivo. The drug candidate, selinexor (KPT-330), is currently in Phase-II/IIb clinical trials for treatment of both hematologic and solid tumors. The present study sought to decipher the mechanisms that render cells either sensitive or resistant to treatment with SINE compounds, represented by KPT-185, an early analogue of KPT-330. Using the human fibrosarcoma HT1080 cell line, resistance to SINE was acquired over a period of 10 months of constant incubation with increasing concentration of KPT-185. Cell viability was assayed by MTT. Immunofluorescence was used to compare nuclear export of TSPs. Fluorescence activated cell sorting (FACS), quantitative polymerase chain reaction (qPCR), and immunoblots were used to measure effects on cell cycle, gene expression, and cell death. RNA from naïve and drug treated parental and resistant cells was analyzed by Affymetrix microarrays. Treatment of HT1080 cells with gradually increasing concentrations of SINE resulted in > 100 fold decrease in sensitivity to SINE cytotoxicity. Resistant cells displayed prolonged cell cycle, reduced nuclear accumulation of TSPs, and similar changes in protein expression compared to parental cells, however the magnitude of the protein expression changes were more significant in parental cells. Microarray analyses comparing parental to resistant cells indicate that a number of key signaling pathways were altered in resistant cells including expression changes in genes involved in adhesion, apoptosis, and inflammation. While the patterns of changes in transcription following drug treatment are similar in parental

  12. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    International Nuclear Information System (INIS)

    Kurooka, Hisanori; Sugai, Manabu; Mori, Kentaro; Yokota, Yoshifumi

    2013-01-01

    Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite

  13. Assessing mRNA nuclear export in mammalian cells by microinjection.

    Science.gov (United States)

    Lee, Eliza S; Palazzo, Alexander F

    2017-08-15

    The nuclear export of mRNAs is an important yet little understood part of eukaryotic gene expression. One of the easiest methods for monitoring mRNA export in mammalian tissue culture cells is through the microinjection of DNA plasmids into the nucleus and monitoring the distribution of the transcribed product over time. Here we describe how to setup a microscope equipped with a micromanipulator used in cell microinjections, and we explain how to perform a nuclear mRNA export assay and obtain the nuclear export rate for any given mRNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Nuclear export policy and regulation for non-proliferation: Federal Republic of Germany

    International Nuclear Information System (INIS)

    Boulanger, Werner.

    1978-01-01

    The nuclear export policy of the Federal Republic of Germany complies with the principle of non-proliferation of nuclear weapons. Already in 1967 the Federal Government stated in a Peace Note that no export was authorised to countries (outside Euratom) which did not comply with the IAEA Safeguards. In the bilateral agreement the Federal Republic signed with Brasil in 1975, emphasis was put on international safeguards and the control exercised on exported materials to avoid any diversion for military purposes. (NEA) [fr

  15. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  16. 10 CFR 110.26 - General license for the export of nuclear reactor components.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF... Denmark Finland France Germany Greece Indonesia Ireland Italy Japan Latvia Lithuania Luxembourg...

  17. 77 FR 51581 - Request for a License To Export Nuclear Grade Graphite

    Science.gov (United States)

    2012-08-24

    ... NUCLEAR REGULATORY COMMISSION Request for a License To Export Nuclear Grade Graphite Pursuant to... 27, 2012, graphite for of nuclear grade graphite to the XMAT424, 11006032. nuclear end use. graphite. Shanghai Institute of Applied Physics in China to test various types of nuclear grade graphite material in...

  18. A study on establishing export system of nuclear related equipments to the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Kim, Seung Soo; Lim, Chae Young; Kim, Hwa Sup; Min, Tae Sik [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-04-01

    In spite of the advanced status in the international nuclear society, exports of domestic nuclear industries to procurement market of the international organizations has been negligible. This study briefly explained the role and the structure of the IAEA. Then, this study surveyed the size of procurement market, major procurement items, and procurement process. This study also gave an export example to the IAEA from Korea Atomic Energy Research Institute for the ease of understanding the procurement process. Based on these surveys and analysis, this study established the goal and strategy for exports of nuclear equipments to the IAEA. Besides, this study surveyed domestic nuclear industries that have potential to export their products to the IAEA. Then, Korea Atomic Energy Research Institute, by a cooperation with Korea Atomic Industrial Forum Inc., held workshop on 'export of nuclear equipments to IAEA' in May 2001 for them. 4 refs., 1 fig., 10 tabs. (Author)

  19. A study on establishing export system of nuclear related equipments to the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Kim, Seung Soo; Lim, Chae Young; Kim, Hwa Sup; Min, Tae Sik [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-04-01

    In spite of the advanced status in the international nuclear society, exports of domestic nuclear industries to procurement market of the international organizations has been negligible. This study briefly explained the role and the structure of the IAEA. Then, this study surveyed the size of procurement market, major procurement items, and procurement process. This study also gave an export example to the IAEA from Korea Atomic Energy Research Institute for the ease of understanding the procurement process. Based on these surveys and analysis, this study established the goal and strategy for exports of nuclear equipments to the IAEA. Besides, this study surveyed domestic nuclear industries that have potential to export their products to the IAEA. Then, Korea Atomic Energy Research Institute, by a cooperation with Korea Atomic Industrial Forum Inc., held workshop on 'export of nuclear equipments to IAEA' in May 2001 for them. 4 refs., 1 fig., 10 tabs. (Author)

  20. A comparative study on export control systems of nuclear technology in ROK and USA

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Jae Woong; Shin, Dong Hoon [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2013-10-15

    Perfect removal of transferred technology is impossible because it is impossible to find all copies of technologies such as files and documents. International community concerns about Terrorists' acquirement of nuclear technologies related to nuclear reactors, enrichment and reprocessing Facilities and heavy water production facilities, which can be used for production of nuclear weapons. Non-state actors as well as concerning countries have tried to possess nuclear technology for developing nuclear weapons. Non-state actors' activities threaten global nuclear security. Korea exported four nuclear power plants to UAE and a research reactor to Jordan. Non-state actors may try to procure nuclear equipment and technology from Korean nuclear industries. Therefore, the export control system should be enhanced for national nuclear security and safety. In this study, the export control system of Korea and the United States were compared concerning to nuclear technology. In summary, controlled activities related to nuclear technology are treated more variously and more diverse activities are controlled in the United States than In Korea. Catch-all control will lose its effectiveness without this. Related to the control of ITT (Intangible Technology Transfer), Korea and the United States are trying to amend the export control regulation. Both of them are trying to control intangible technology transfers effectively. Revised Foreign Trade Act in Korea is expected to introduce a more rigorous system of nuclear technology controls. It focuses on nationality rather than residence. The revised law may face into other problems such as dual nationals like as the United States. However, this satisfies legislative requirements for control of a deemed export. The revised law will enter into force in 2014. Accurate meanings of technology and export will be defined soon in the enforcement decree and the public notice before 2014. However, it is hard to revise the definition

  1. A comparative study on export control systems of nuclear technology in ROK and USA

    International Nuclear Information System (INIS)

    Tae, Jae Woong; Shin, Dong Hoon

    2013-01-01

    Perfect removal of transferred technology is impossible because it is impossible to find all copies of technologies such as files and documents. International community concerns about Terrorists' acquirement of nuclear technologies related to nuclear reactors, enrichment and reprocessing Facilities and heavy water production facilities, which can be used for production of nuclear weapons. Non-state actors as well as concerning countries have tried to possess nuclear technology for developing nuclear weapons. Non-state actors' activities threaten global nuclear security. Korea exported four nuclear power plants to UAE and a research reactor to Jordan. Non-state actors may try to procure nuclear equipment and technology from Korean nuclear industries. Therefore, the export control system should be enhanced for national nuclear security and safety. In this study, the export control system of Korea and the United States were compared concerning to nuclear technology. In summary, controlled activities related to nuclear technology are treated more variously and more diverse activities are controlled in the United States than In Korea. Catch-all control will lose its effectiveness without this. Related to the control of ITT (Intangible Technology Transfer), Korea and the United States are trying to amend the export control regulation. Both of them are trying to control intangible technology transfers effectively. Revised Foreign Trade Act in Korea is expected to introduce a more rigorous system of nuclear technology controls. It focuses on nationality rather than residence. The revised law may face into other problems such as dual nationals like as the United States. However, this satisfies legislative requirements for control of a deemed export. The revised law will enter into force in 2014. Accurate meanings of technology and export will be defined soon in the enforcement decree and the public notice before 2014. However, it is hard to revise the definition of export

  2. Decision support for selecting exportable nuclear technology using the analytic hierarchy process: A Korean case

    International Nuclear Information System (INIS)

    Lee, Deok Joo; Hwang, Jooho

    2010-01-01

    The Korean government plans to increase strategically focused R and D investment in some promising nuclear technology areas to create export opportunities of technology in a global nuclear market. The purpose of this paper is to present a decision support process for selecting promising nuclear technology with the perspective of exportability by using the AHP based on extensive data gathered from nuclear experts in Korea. In this study, the decision criteria for evaluating the export competitiveness of nuclear technologies were determined, and a hierarchical structure for the decision-making process was systematically developed. Subsequently relative weights of decision criteria were derived using AHP methodology and the export competitiveness of nuclear technology alternatives was quantified to prioritize them. We discuss the implications of our results with a viewpoint toward national nuclear technology policy.

  3. Korean system of export control to support the commercial nuclear transfer to UAE

    International Nuclear Information System (INIS)

    Cho, Young Ho

    2011-01-01

    In December 2009, the Republic of Korea won the contract to build 4 1,400 MW nuclear power reactors worth USD 20 billion in the UAE. The states-owned KEPCO will complete the turnkey project to the UAE including design, engineering, construction, nuclear fuel, operations, maintenance and technical support. Since sensitive nuclear technologies convertible to military purpose can be spread by the transfer of commercial nuclear power plant, it is essential prerequisite to implement nuclear export control tenaciously and effectively. About twenty years have passed since the Republic of Korea introduced export control system in domestic laws and regulations. Marking a major historical milestone in 2009 by ranking among global nuclear suppliers, the Korean government made a major step forward in export control framework to support its next nuclear export goal. (orig.)

  4. Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    2014-03-01

    Full Text Available Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV transcripts depends on the nuclear export factor (NXF1 pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts.

  5. Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

    Directory of Open Access Journals (Sweden)

    Marriott Susan J

    2007-12-01

    Full Text Available Abstract Background The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS. We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins. Results We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284 within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35. Conclusion This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284

  6. Nuclear power, nuclear exports and the non-proliferation of nuclear weapons

    International Nuclear Information System (INIS)

    Hildenbrand, G.

    1977-01-01

    Developed and developing countries alike unfortunately have no other options in replacing oil in electricity generation than to use coal or nuclear energy. As far as the supplier countries are concerned, there is no doubt that nobody is interested in adding to the proliferation of nuclear weapons. On the other hand, the future electricity requirement in the developing countries, especially the need for nuclear power plants, represents a considerable market in the medium and long term which the supplier countries cannot simply ignore because they must seek to secure their export shares in order to protect jobs at home. For the receiver countries it is a matter of principle to achieve the highest possible degree of independence in energy generation so as to be able to guarantee continuity of supply. The interest in building up national fuel cycle activities is also closely linked with the creation of jobs in the receiver countries and with the efforts of these countries to straighten out their balance of payments situation. (orig.) [de

  7. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

    Science.gov (United States)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

    International Nuclear Information System (INIS)

    Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

    2005-01-01

    The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

  9. Korea nuclear exports: Why did the Koreans win the UAE tender? Will Korea achieve its goal of exporting 80 nuclear reactors by 2030?

    International Nuclear Information System (INIS)

    Berthelemy, Michel; Leveque, Francois

    2011-01-01

    The success of Korea in winning, in December 2009, a USD 18.6 billion nuclear tender in the United Arab Emirates (UAE) has led to a growing interest in the organization and strengths of the Korean nuclear industry. In this paper, we present the main economic and political factors that explain the success of the Korean consortium. In particular, thanks to an active national program of Nuclear Power Plant (NPP) construction, Korea has developed distinct competitive advantages in terms of low cost, high credibility and high performance. At the same time, due to the important barriers to enter into the nuclear export market in the UAE, Korea has had to sacrifice its profit margin and has benefited from a strong political support from its government through export financing. More importantly, Korea's success is also due to its alliance with Westinghouse and the support of the US diplomacy. Subsequently, we show that while Korea has recently experienced setbacks in nuclear tenders, it will most certainly try to win in the short run a second nuclear tender with another aggressive price. In the longer run, Korea could take a growing share of the international market for NPPs. However, the extent to which Korea can achieve its long term export target will depend upon its capacity to finance nuclear export through export credits and upon the development of its alliance with Westinghouse. It is important to note that this paper was written before the Fukushima nuclear disaster. The scale of the human and environmental consequences of this accident are still unknown, and will undoubtedly have short and long term consequences on nuclear safety requirements and public attitude toward nuclear energy, which will most certainly impact the outlooks for nuclear new-builds. (authors)

  10. Nuclear safety aspects of exported replicate nuclear power plants and associated problems

    International Nuclear Information System (INIS)

    Kern, H.G.

    1978-01-01

    The standardization of the export nuclear power plant is being pursued with the concept of replication. This concept entails using another exported Nuclear Power Plant (NPP) as the base design and adapting it to a new site. The general ground rule applied to this concept is upgrading the design where necessary and duplicating the design where it is superior. Such continuous improvement will result in a standard export NPP that incorporates design features which will make it essentially acceptable for any suitable site. The advantages of replication are, therefore, boundless. However, the replication mode requires superior design control by the engineer to assure that only improvements alter the base design. With this concept, the replicating engineer is essentially assigned the responsiblity of safeguarding the standard export plant design. He is delegated the task of filtering the design such that only the conservative aspects prevail. Tight control of design changes via properly administered procedures is necessary to assure that no unforeseen compromises are made in designs which have already achieved optimization. Techniques to accomplish successful replication include, among others, the use of PCNs, system cognizant engineers, design verfication review, and the participation of all engineering disciplines in the development of the project schedule. (author)

  11. Development of Export Control Comprehensive Management Model for Nuclear Power Plants and Others Projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chansuh; Seo, Hana; Choi, Sundo [Korea Institute of Nuclear Nonproliferation And Control, Daejeon (Korea, Republic of)

    2014-05-15

    It is required that there are lots of managements of care and concern if the project contains strategic items such as NPPs. The Korean nuclear industry and its related companies, such as the Korea Hydro and Nuclear Power (KHNP), are promoting greater exports of NPPs. It is likely that Korea will export more this technology to newcomer states in the future. As a result, the ROK has been improving its export control management system for NPPs. In keeping with this national effort, Korea Institute of Nuclear Nonproliferation And Control (KINAC) developed comprehensive export control management model for NPPs and other projects, in preparation for this projected growth in the industry. This model also applies to the nuclear export case of the UAE, aims to manage the project from bidding to the end of the contract. The recent Export Licensing of Nuclear Facility Technology was reflected in the Notice on Export and Import of Strategic Items in January 2014. Through this license, the large-scale project legislation framework was established. It can also minimize nonproliferation concerns of the international community through strict management. It is expected that the Korea will be able to enhance transparency and secure the nuclear use, while meeting nonproliferation purpose.

  12. Development of Export Control Comprehensive Management Model for Nuclear Power Plants and Others Projects

    International Nuclear Information System (INIS)

    Lee, Chansuh; Seo, Hana; Choi, Sundo

    2014-01-01

    It is required that there are lots of managements of care and concern if the project contains strategic items such as NPPs. The Korean nuclear industry and its related companies, such as the Korea Hydro and Nuclear Power (KHNP), are promoting greater exports of NPPs. It is likely that Korea will export more this technology to newcomer states in the future. As a result, the ROK has been improving its export control management system for NPPs. In keeping with this national effort, Korea Institute of Nuclear Nonproliferation And Control (KINAC) developed comprehensive export control management model for NPPs and other projects, in preparation for this projected growth in the industry. This model also applies to the nuclear export case of the UAE, aims to manage the project from bidding to the end of the contract. The recent Export Licensing of Nuclear Facility Technology was reflected in the Notice on Export and Import of Strategic Items in January 2014. Through this license, the large-scale project legislation framework was established. It can also minimize nonproliferation concerns of the international community through strict management. It is expected that the Korea will be able to enhance transparency and secure the nuclear use, while meeting nonproliferation purpose

  13. Nuclear Successor States of the Soviet Union, Nuclear Weapon and Sensitive Export Status Report

    Science.gov (United States)

    1994-05-01

    international advisory group composed of: Valentin Alexandrov Ministry of Foreign Affairs, Minsk Alexander Bolsunovsky Institute of Biophysics, Krasnoyarsk Oleg...Center for Nonproliferation and Export Control, Minsk Alexander Pikayev Inst. of World Economy and Intl. Relations, Moscow Anatoly Scherba Ministry of...Bulletin of the Atomic Scientists, March/April 1994; A. Pikayev and A. Savelyev , "The USSR’s Nuclear Might: On Land, At Sea, At Air," Nezavisimaya Gazeta

  14. The formation of nuclear export control in Azerbaijan

    International Nuclear Information System (INIS)

    Garibov, A.A.

    2003-01-01

    Full text: The controlling process of exporting and importing on Azerbaijan borders is being carried out by two state organizations. 1.Border Guard Department; 2.Azerbaijan State Customs Committee. The officers of these organizations have no enough necessary experience and knowledge dealing with the legal and illegal trafficking. There were not special educational institutions in order to train personals for both of these organizations made newly. So there's difference between the professions of the majority of the employees, that's why some of the employees follow the instructions linking to the normative documents while passing the border. When trafficking nuclear and dual-use items officially the controller and other employees should look through the list of all and know them how to behave and to make official, the characteristic parameters of the materials, and the instruction of monitoring. In order to realize all works pointed, the employees of Border Guard Department and Customs Control Check Points have to attend special courses. The employees of both organizations are frequently changed that's why studying courses are to be organized. The analysis of studying considered that will be realized shows mainly there may be two student groups. Mainly, the Institute of Radiation Problems of ANAS (Azerbaijan National Academy of Sciences) as the expert laboratory takes part in. On the borders of Azerbaijan Republic the dual-use items and equipment having the type of isotope sources being utilized in the technological process are mainly being transported. In the materials presented the results and the solution of the problems dealing with realizing the controlling expert system of nuclear materials in the existing control checkpoints due to the international standards have been given

  15. Define rules for the exporter and importer of minerals or ores containing nuclear elements

    International Nuclear Information System (INIS)

    1969-01-01

    The present resolution establishes regulations for the exporter of minerals or ores containing associated nuclear elements, and for the importer of chemical compounds of technical purity grade, containing a quantity of fissile of fertile materials equal to the existent in the exported material

  16. The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export.

    Directory of Open Access Journals (Sweden)

    Tohru Minamino

    2016-03-01

    Full Text Available The bacterial flagellar type III export apparatus utilizes ATP and proton motive force (PMF to transport flagellar proteins to the distal end of the growing flagellar structure for self-assembly. The transmembrane export gate complex is a H+-protein antiporter, of which activity is greatly augmented by an associated cytoplasmic ATPase complex. Here, we report that the export gate complex can use sodium motive force (SMF in addition to PMF across the cytoplasmic membrane to drive protein export. Protein export was considerably reduced in the absence of the ATPase complex and a pH gradient across the membrane, but Na+ increased it dramatically. Phenamil, a blocker of Na+ translocation, inhibited protein export. Overexpression of FlhA increased the intracellular Na+ concentration in the presence of 100 mM NaCl but not in its absence, suggesting that FlhA acts as a Na+ channel. In wild-type cells, however, neither Na+ nor phenamil affected protein export, indicating that the Na+ channel activity of FlhA is suppressed by the ATPase complex. We propose that the export gate by itself is a dual fuel engine that uses both PMF and SMF for protein export and that the ATPase complex switches this dual fuel engine into a PMF-driven export machinery to become much more robust against environmental changes in external pH and Na+ concentration.

  17. The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export.

    Science.gov (United States)

    Minamino, Tohru; Morimoto, Yusuke V; Hara, Noritaka; Aldridge, Phillip D; Namba, Keiichi

    2016-03-01

    The bacterial flagellar type III export apparatus utilizes ATP and proton motive force (PMF) to transport flagellar proteins to the distal end of the growing flagellar structure for self-assembly. The transmembrane export gate complex is a H+-protein antiporter, of which activity is greatly augmented by an associated cytoplasmic ATPase complex. Here, we report that the export gate complex can use sodium motive force (SMF) in addition to PMF across the cytoplasmic membrane to drive protein export. Protein export was considerably reduced in the absence of the ATPase complex and a pH gradient across the membrane, but Na+ increased it dramatically. Phenamil, a blocker of Na+ translocation, inhibited protein export. Overexpression of FlhA increased the intracellular Na+ concentration in the presence of 100 mM NaCl but not in its absence, suggesting that FlhA acts as a Na+ channel. In wild-type cells, however, neither Na+ nor phenamil affected protein export, indicating that the Na+ channel activity of FlhA is suppressed by the ATPase complex. We propose that the export gate by itself is a dual fuel engine that uses both PMF and SMF for protein export and that the ATPase complex switches this dual fuel engine into a PMF-driven export machinery to become much more robust against environmental changes in external pH and Na+ concentration.

  18. Nuclear Non-Proliferation and Export Control in the Republic of Croatia

    International Nuclear Information System (INIS)

    Valcic, I.; Prah, M.; Mikec, N.

    2006-01-01

    In accordance with its internationally accepted obligations, the Republic of Croatia is actively implementing principles of non-proliferation and export control of nuclear materials and/or equipment. The article deals with treaties, conventions, agreements and other international arrangements that are creating certain obligation for Republic of Croatia related to nuclear non-proliferation. The most important are the Treaty on the Non-proliferation of Nuclear Weapons, the Convention on the Physical Protection of Nuclear Material, the Agreement between the Republic of Croatia and the International Atomic Energy Agency for the Application of Safeguards with Protocol, the Protocol Additional to the Agreement Between the Republic of Croatia and the International Atomic Energy Agency for the Application of Safeguards, the Comprehensive Nuclear Test-Ban Treaty, the NSG Guidelines for the Export of Nuclear Material, Equipment and Technology and NSG Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Materials, Software and Related Technology. In addition the article describes a national regulative framework, the basis for conducting activities in nuclear material control, export control of dual-use items as well as non-proliferation of the weapons of mass destruction. Details are given about the Nuclear Safety Act, the Act on Liability for Nuclear Damage, the Act on Export of Dual-Use Items, the Decree on the List of Dual-Use Items, the Law on Production, Repair and Trade in Arms and Military Equipment and the Decree specifying goods subject to export and import licenses. (author)

  19. Analysis of nuclear export control system and implementing international nonproliferation regime in China

    International Nuclear Information System (INIS)

    Kim, J. S.; Lee, J. S.; Ahn, J. S.; Kim, B. G.; Min, K. S.

    2000-01-01

    China's exporting behaviour of nuclear items had been disconnected from the international non-proliferation regime such as IAEA safeguards and export control related with peaceful use of nuclear energy since 1970s. Especially, China had been one of principle suppliers of nuclear facility and technologies to Pakistan and Iran which had developed nuclear weapon programs. On the other hand, according to the rapid growth of economic scale after China began to open to the world, an active program for nuclear power plant as an electricity source had established. This means that China have surfaced as a big market to Korean nuclear industries. Regarding this, the paper dealt with the nuclear export control matters, i.e. the history of nuclear export control system and analyzed on background of enforcement of U.S.-China Nuclear Cooperation Agreement that had been apolitical issue between U.S. and China. Prospects toward conforming its nuclear export policies, laws and regulations to international standards also analyzed in results

  20. [Polyadenylated RNA and mRNA export factors in extrachromosomal nuclear domains of vitellogenic oocytes of the insect Tenebrio molitor].

    Science.gov (United States)

    Bogoliubov, D S; Kiselev, A M; Shabel'nikov, S V; Parfenov, V N

    2012-01-01

    The nucleus ofvitellogenic oocytes of the yellow mealworm, Tenebrio molitor, contains a karyosphere that consists of the condensed chromatin embedded in an extrachromosomal fibrogranular material. Numerous nuclear bodies located freely in the nucleoplasm are also observed. Amongst these bodies, counterparts of nuclear speckles (= interchromatin granule clusters, IGCs) can be identified by the presence of the marker protein SC35. Microinjections of fluorescently tagged methyloligoribonucleotide probes 2'-O-Me(U)22, complementary to poly(A) tails of RNAs, revealed poly(A)+ RNA in the vast majority of IGCs. We found that all T. molitor oocyte IGCs contain heterogeneous ribonucleoprotein (hnRNP) core protein Al that localizes to IGCs in an RNA-dependent manner. The extrachromosomal material of the karyosphere and a part of nucleoplasmic IGCs also contain the adapter protein Aly that is known to provide a link between pre-mRNA splicing and mRNA export. The essential mRNA export factor/receptor NXF1 was observed to colocalize with Aly. In nucleoplasmic IGCs, NXF1 was found to localize in an RNA-dependent manner whereas it is RNA-independently located in the extrachromosomal material of the karyosphere. We believe our data suggest on a role of the nucleoplasmic IGCs in mRNA biogenesis and retention in a road to nuclear export.

  1. Study on international publicity and export strategy establishment of nuclear technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Bok; Choi, C.O.; Park, K. B.; Chang, M. H.; Kim, K. K.; Yang, M. S.; Jung, I. H.; Kim, K. P.; Wu, J. S.; Jang, C. I.; Han, B. O.; Sim, J. H.; Chung, M.; Chung, J.K

    1999-05-01

    The objective of this study is to devise a proper measure for international publicity and technology export strategy. Analysed and summaries in detail are other countries nuclear policy trend and the current technology development status of Korea Standard Nuclear Plant that we developed on our own technology, design and construction technology for research reactor, System-integrated Modular Advanced Reactor of which design is in progress, Direct use of Spent PWR Fuel in CANDU Reactors, and Radioisotopes. Based on that, the measures are proposed for the export industrialization of nuclear technology and establishment of the export basis. Also the international nuclear cooperation and publicity strategy are suggested to support the technology export basis. By surveying the world nuclear status, the direction for the international cooperation and publicity is settled and the specific publicity strategy is proposed for the cooperation with IAEA and multi-countries and the establishment of the nuclear technology export basis. As part of this project, the panel on major technologies such as Korea Standard Nuclear Plant, HANARO, and System-integrated Modular Advanced Reactor was displayed successfully at the IAEA meeting, which contribute much to the publicity of our nuclear technology to the international nuclear society. (author)

  2. The Cellular Distribution of RanGAP1 Is Regulated by CRM1-Mediated Nuclear Export in Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Keith Cha

    Full Text Available The Ran GTPase activating protein RanGAP1 plays an essential role in nuclear transport by stimulating RanGTP hydrolysis in the cytoplasmic compartment. In mammalian cells, unmodified RanGAP1 is predominantly cytoplasmic, whereas modification by small ubiquitin-related modifier protein (SUMO targets RanGAP1 to the cytoplasmic filaments of nuclear pore complex (NPC. Although RanGAP1 contains nine putative nuclear export signals and a nuclear localization signal, little is known if RanGAP1 shuttles between the nuclear and cytoplasmic compartments and how its primary localization in the cytoplasm and at the NPC is regulated. Here we show that inhibition of CRM1-mediated nuclear export using RNAi-knockdown of CRM1 and inactivation of CRM1 by leptomycin B (LMB results in nuclear accumulation of RanGAP1. LMB treatment induced a more robust redistribution of RanGAP1 from the cytoplasm to the nucleoplasm compared to CRM1 RNAi and also uniquely triggered a decrease or loss of RanGAP1 localization at the NPC, suggesting that LMB treatment is more effective in inhibiting CRM1-mediated nuclear export of RanGAP1. Our time-course analysis of LMB treatment reveals that the NPC-associated RanGAP1 is much more slowly redistributed to the nucleoplasm than the cytoplasmic RanGAP1. Furthermore, LMB-induced nuclear accumulation of RanGAP1 is positively correlated with an increase in levels of SUMO-modified RanGAP1, suggesting that SUMOylation of RanGAP1 may mainly take place in the nucleoplasm. Lastly, we demonstrate that the nuclear localization signal at the C-terminus of RanGAP1 is required for its nuclear accumulation in cells treated with LMB. Taken together, our results elucidate that RanGAP1 is actively transported between the nuclear and cytoplasmic compartments, and that the cytoplasmic and NPC localization of RanGAP1 is dependent on CRM1-mediated nuclear export.

  3. The National Implementation of Nuclear Export Controls: Developing a Best Practices Model

    Energy Technology Data Exchange (ETDEWEB)

    Viski, Andrea [European University Institute, Department of Law, Badia Fiesolana, S.Domenico di Fiesole, Firenze (Italy)

    2011-12-15

    The nuclear renaissance promises significant benefits to the international community, but also raises security challenges, particularly relating to the trade of nuclear materials and equipment. The objective of this paper is to examine how supply-side non-proliferation efforts can be strengthened by developing a best practices model for national nuclear export control implementation. In order to achieve this goal, nuclear export control measures identified by the 1540 Committee will be used as a framework from which a best practices model can be formed. Such a model concentrates specifically on national legislation and enforcement measures delineated by the Committee in order to bring countries in accordance with international law. Developing a best practices model seeks to deliver an ideal process for national export control law actualization in order to encourage the peaceful development of nuclear energy and develop the infrastructure and framework for precluding nuclear proliferation.

  4. Conditional Depletion of Nuclear Proteins by the Anchor Away System (ms# CP-10-0125)

    Science.gov (United States)

    Fan, Xiaochun; Geisberg, Joseph V.; Wong, Koon Ho; Jin, Yi

    2011-01-01

    Nuclear proteins play key roles in the regulation of many important cellular processes. In Saccharomyces cerevisiae, many genes encoding nuclear proteins are essential. Here we describe a method termed Anchor Away that can be used to conditionally and rapidly deplete nuclear proteins of interest. It involves conditional export of the protein of interest out of the nucleus and its subsequent sequestration in the cytoplasm. This method can be used to simultaneously deplete multiple proteins from nucleus. PMID:21225637

  5. A study on the revision of nuclear safety act to build the foundation of nuclear export and import control system in Korea

    International Nuclear Information System (INIS)

    Yang, Seung Hyo; Choi, Sun Do

    2012-01-01

    Nuclear related items require export and import control beyond the multilateral export control system according to Safeguard Agreement, Additional Protocol and bilateral agreements. Besides Korea as a nuclear supplier is needed to actively cope with its export control system, which is being reinforced internationally. In regard to this trend, this study drew the revision plan of present Nuclear Safety Act to found the nuclear export and import control system in Korea by examining the related legislations and analyzing the implementation status of nuclear export and import control

  6. A study on the revision of nuclear safety act to build the foundation of nuclear export and import control system in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Seung Hyo; Choi, Sun Do [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2012-10-15

    Nuclear related items require export and import control beyond the multilateral export control system according to Safeguard Agreement, Additional Protocol and bilateral agreements. Besides Korea as a nuclear supplier is needed to actively cope with its export control system, which is being reinforced internationally. In regard to this trend, this study drew the revision plan of present Nuclear Safety Act to found the nuclear export and import control system in Korea by examining the related legislations and analyzing the implementation status of nuclear export and import control.

  7. Nuclear transport of heat shock proteins in stressed cells

    International Nuclear Information System (INIS)

    Chughtai, Zahoor Saeed

    2001-01-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or β-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-β-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single β-importin gene. With this assay I have identified Nmd5p as a β-importin required to concentrate Star-β-galactosidase in nuclei of stationary phase cells. (author)

  8. Nuclear transport of heat shock proteins in stressed cells

    Energy Technology Data Exchange (ETDEWEB)

    Chughtai, Zahoor Saeed

    2001-07-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or {beta}-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-{beta}-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single {beta}-importin gene. With this assay I have identified Nmd5p as a {beta}-importin required to concentrate Star-{beta}-galactosidase in nuclei of stationary phase cells. (author)

  9. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Science.gov (United States)

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  10. In Vitro Reconstitution of Functional Type III Protein Export and Insights into Flagellar Assembly.

    Science.gov (United States)

    Terashima, Hiroyuki; Kawamoto, Akihiro; Tatsumi, Chinatsu; Namba, Keiichi; Minamino, Tohru; Imada, Katsumi

    2018-06-26

    The type III secretion system (T3SS) forms the functional core of injectisomes, protein transporters that allow bacteria to deliver virulence factors into their hosts for infection, and flagella, which are critical for many pathogens to reach the site of infection. In spite of intensive genetic and biochemical studies, the T3SS protein export mechanism remains unclear due to the difficulty of accurate measurement of protein export in vivo Here, we developed an in vitro flagellar T3S protein transport assay system using an inverted cytoplasmic membrane vesicle (IMV) for accurate and controlled measurements of flagellar protein export. We show that the flagellar T3SS in the IMV fully retains export activity. The flagellar hook was constructed inside the lumen of the IMV by adding purified component proteins externally to the IMV solution. We reproduced the hook length control and export specificity switch in the IMV consistent with that seen in the native cell. Previous in vivo analyses showed that flagellar protein export is driven by proton motive force (PMF) and facilitated by ATP hydrolysis by FliI, a T3SS-specific ATPase. Our in vitro assay recapitulated these previous in vivo observations but furthermore clearly demonstrated that even ATP hydrolysis by FliI alone can drive flagellar protein export. Moreover, this assay showed that addition of the FliH 2 /FliI complex to the assay solution at a concentration similar to that in the cell dramatically enhanced protein export, confirming that the FliH 2 /FliI complex in the cytoplasm is important for effective protein transport. IMPORTANCE The type III secretion system (T3SS) is the functional core of the injectisome, a bacterial protein transporter used to deliver virulence proteins into host cells, and bacterial flagella, critical for many pathogens. The molecular mechanism of protein transport is still unclear due to difficulties in accurate measurements of protein transport under well-controlled conditions in

  11. Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export.

    Science.gov (United States)

    Larsen, Sean; Bui, Steven; Perez, Veronica; Mohammad, Adeba; Medina-Ramirez, Hilario; Newcomb, Laura L

    2014-08-28

    Influenza is a segmented negative strand RNA virus. Each RNA segment is encapsulated by influenza nucleoprotein and bound by the viral RNA dependent RNA polymerase (RdRP) to form viral ribonucleoproteins responsible for RNA synthesis in the nucleus of the host cell. Influenza transcription results in spliced mRNAs (M2 and NS2), intron-containing mRNAs (M1 and NS1), and intron-less mRNAs (HA, NA, NP, PB1, PB2, and PA), all of which undergo nuclear export into the cytoplasm for translation. Most cellular mRNA nuclear export is Nxf1-mediated, while select mRNAs utilize Crm1. Here we inhibited Nxf1 and Crm1 nuclear export prior to infection with influenza A/Udorn/307/1972(H3N2) virus and analyzed influenza intron-less mRNAs using cellular fractionation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined direct interaction between Nxf1 and influenza intron-less mRNAs using immuno purification of Nxf1 and RT-PCR of associated RNA. Inhibition of Nxf1 resulted in less influenza intron-less mRNA export into the cytoplasm for HA and NA influenza mRNAs in both human embryonic kidney cell line (293 T) and human lung adenocarcinoma epithelial cell line (A549). However, in 293 T cells no change was observed for mRNAs encoding the components of the viral ribonucleoproteins; NP, PA, PB1, and PB2, while in A549 cells, only PA, PB1, and PB2 mRNAs, encoding the RdRP, remained unaffected; NP mRNA was reduced in the cytoplasm. In A549 cells NP, NA, HA, mRNAs were found associated with Nxf1 but PA, PB1, and PB2 mRNAs were not. Crm1 inhibition also resulted in no significant difference in PA, PB1, and PB2 mRNA nuclear export. These results further confirm Nxf1-mediated nuclear export is functional during the influenza life cycle and hijacked for select influenza mRNA nuclear export. We reveal a cell type difference for Nxf1-mediated nuclear export of influenza NP mRNA, a reminder that cell type can influence molecular mechanisms. Importantly, we

  12. One recommendation of nuclear power export. GDP model application to the countries which expressed nuclear power introduction and consideration

    International Nuclear Information System (INIS)

    Iida, Tekehiko

    2010-01-01

    South Korea has been excited in nuclear business after the success in the contract to build nuclear power plants in UAE. Since more than 60 countries expressed nuclear power introduction and new countries were on the rise with exporting reactor technology accumulated, new era over nuclear renaissance seems to begin. This article at first classified countries, which expressed nuclear power introduction, with an economic level of GDP per capita. Then each classified country's requirements of nuclear power introduction were taken into consideration such as economic development, consumption pattern and technology attitude. As a result recommendation of nuclear power export was proposed. Different approach to each country targeted was suggested as shown in 'nuclear power GDP model'. (T. Tanaka)

  13. Nuclear fuels imports and exports of the Federal Republic of Germany 1989

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The statistics compiled by the Federal Office for the Economy (Bundesamt fuer Wirtschaft) on behalf of the German Federal Ministry for the Environment, Nature Conservation and Reactor Safety of the imports and exports of nuclear fuels and source material in 1989 show a drop in imports by 29.5% and a considerable increase in exports by 104%. For comparison, the relevant figures of the preceding year are given in brackets throughout this statistical survey. (orig.) [de

  14. CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization

    International Nuclear Information System (INIS)

    Neyton, Sophie; Lespinasse, Francoise; Lahaye, Francois; Staccini, Pascal; Paquis-Flucklinger, Veronique; Santucci-Darmanin, Sabine

    2007-01-01

    MSH4 and MSH5 are members of the MutS homolog family, a conserved group of proteins involved in DNA mismatch correction and homologous recombination. Although several studies have provided compelling evidences suggesting that MSH4 and MSH5 could act together in early and late stages of meiotic recombination, their precise roles are poorly understood and recent findings suggest that the human MSH4 protein may also exert a cytoplasmic function. Here we show that MSH4 is present in the cytoplasm and the nucleus of both testicular cells and transfected somatic cells. Confocal studies on transfected cells provide the first evidence that the subcellular localization of MSH4 is regulated, at least in part, by an active nuclear export pathway dependent on the exportin CRM1. We used deletion mapping and mutagenesis to define two functional nuclear export sequences within the C-terminal part of hMSH4 that mediate nuclear export through the CRM1 pathway. Our results suggest that CRM1 is also involved in MSH5 nuclear export. In addition, we demonstrate that dimerization of MSH4 and MSH5 facilitates their nuclear localization suggesting that dimerization may regulate the intracellular trafficking of these proteins. Our findings suggest that nucleocytoplasmic traffic may constitute a regulatory mechanism for MSH4 and MSH5 functions

  15. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

    Science.gov (United States)

    2014-01-01

    Background Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. Conclusions KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma. PMID:25022346

  16. Analysis of World Nuclear Market and Strategy of Korean NPP's Competitiveness Improvement for Exportation

    International Nuclear Information System (INIS)

    Choi, Jae Young; Jeong, Yong Hoon; Roh, Seungkook; Chang, Soon Heung

    2016-01-01

    China, India and USA (nuclear adopted countries) are planning tremendous number of NPPs to meet their increasing electricity demand and Saudi Arabia, Vietnam (nuclear adopting countries) are also planning to include nuclear power in their energy mix as a long-term plan. Korea has exported 4 units of APR1400 to the UAE in December, 2009. Korea became sixth NPP supplier country and our economic feasibility and safety features were started to evaluate worldwide. Nuclear industries became a new driver of Korea’s export and nuclear industries in Korea are now expecting another NPP export to Middle-eastern countries, including UAE and Saudi Arabia, based on the first-mover’s advantage at the UAE. In 2000s, five countries (Japan, USA, France, Russia and Korea), which are able to build NPP, focused on NPP export more than domestic construction. Global trend of world nuclear market changed rapidly, especially after NPP export to the UAE. By the global trend, hegemony of nuclear market migrated from supplier country to buyer country. Nuclear companies started cooperating rather than competing. Financing to developing countries become more important. In general, one of the considerable combinations is Korea-Japan-USA alliance. Korea is in charge of EPC, Japan supports financing and deficient technology (with USA partner), and Japan-USA handles fuel supply and back-end fuel cycle based on new agreed terms of ROK-US Nuclear Cooperation Agreement. This combination was judged to best way to collaborate with global companies. Paying attention to many delayed (or potentially delayed) constructions from Russia, intercepting the construction work will be available in case of contracted countries. Korea can emphasize the short construction time, high responsiveness and mild/equal diplomatic position to the target countries

  17. China sets sights on exporting an affordable nuclear solution

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, David [NucNet, Bruessel (Belgium)

    2016-03-15

    Since the Fukushima-Daiichi accident in 2011 few western countries have been building nuclear reactors. China, however, seems to be going on something of a spree, sensing a solution for pollution at home - and unprecedented commercial opportunities abroad. There might be a general feeling in the industry that nuclear energy is on the wane in the West, but the same industry is casting increasingly envious glances to the East. A minimum of 60 nuclear power reactors are expected to start up in China over the next decade. By 2050, nuclear power should exceed 350 GW in China, with about 400 new nuclear reactors and total nuclear investment of over a trillion dollars.

  18. Final report of the 2. committee of investigation of the 11. legislative period. Nuclear exports

    International Nuclear Information System (INIS)

    1990-01-01

    On the subject of 'nuclear exports' the Committee dealt with political and legal principles of the Federal Government's nuclear export policy, particularly questions concerning the Non-Proliferation Treaty, and scientific-technical cooperation of the FRG with other countries, especially Argentina, Brazil, India, and Pakistan. Individual export transactions were then investigated, followed by a general assessment of the FRG's nuclear policy. - Concerning non-proliferation policy there have been certain administrative weaknesses in converting control measures into practice. Remedy is expected from the duty of terms to report deliveries punctually and completely and subsequent supervision. - The illegal transactions with India and Pakistan require improvements in the legal instruments, in the execution of administrative measures, and in border controls. Decisive steps have been introduced. (HSCH) [de

  19. Export and import provisions for nuclear materials and power plants, from the legal point of view

    International Nuclear Information System (INIS)

    Shapar, H.K.

    1975-01-01

    This paper provides a general review of the legal bases for and the administrative procedures involved in the export and import licensing of nuclear power reactors, fuels, and other nuclear materials by the United States. The basic statutory provisions and requirements are briefly described, and the requirement of an agreement for cooperation reviewed. The regulations of the Nuclear Regulatory Commission are covered in greater detail as they apply to the export and import of power reactors, nuclear fuels, source materials and byproduct materials. The intra-governmental procedures for review of an application for an export license are described in detail. Problems encountered in the administration of the law and regulations are described and the methods of resolving them are noted. The paper concludes with a brief account of three current topics, 1) the preparation of an environmental impact statement for export programs, 2) the situation with respect to the export licensing of component parts of reactors by the U.S. Department of Commerce, and 3) the shipment of plutonium by air. (orig.) [de

  20. Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA-Helicase as for mRNA Export.

    Science.gov (United States)

    Neumann, Bettina; Wu, Haijia; Hackmann, Alexandra; Krebber, Heike

    2016-01-01

    The DEAD-box RNA-helicase Dbp5/Rat8 is known for its function in nuclear mRNA export, where it displaces the export receptor Mex67 from the mRNA at the cytoplasmic side of the nuclear pore complex (NPC). Here we show that Dbp5 is also required for the nuclear export of both pre-ribosomal subunits. Yeast temperature-sensitive dbp5 mutants accumulate both ribosomal particles in their nuclei. Furthermore, Dbp5 genetically and physically interacts with known ribosomal transport factors such as Nmd3. Similar to mRNA export we show that also for ribosomal transport Dbp5 is required at the cytoplasmic side of the NPC. However, unlike its role in mRNA export, Dbp5 does not seem to undergo its ATPase cycle for this function, as ATPase-deficient dbp5 mutants that selectively inhibit mRNA export do not affect ribosomal transport. Furthermore, mutants of GLE1, the ATPase stimulating factor of Dbp5, show no major ribosomal export defects. Consequently, while Dbp5 uses its ATPase cycle to displace the export receptor Mex67 from the translocated mRNAs, Mex67 remains bound to ribosomal subunits upon transit to the cytoplasm, where it is detectable on translating ribosomes. Therefore, we propose a model, in which Dbp5 supports ribosomal transport by capturing ribosomal subunits upon their cytoplasmic appearance at the NPC, possibly by binding export factors such as Mex67. Thus, our findings reveal that although different ribonucleoparticles, mRNAs and pre-ribosomal subunits, use shared export factors, they utilize different transport mechanisms.

  1. Communications received from Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received notes verbales to the export of nuclear material, equipment and technology from the following Permanent Missions to the International Atomic Energy Agency: notes verbales dated 1 March 1994 from the Permanent Missions of Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Japan, the Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, the United States of America; and a note verbale dated 12 March 1994 from the Permanent Mission of Romania. The purpose of these notes verbales is to provide further information on these Governments' nuclear export policies and practices

  2. 1987 nuclear fuel imports and exports of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    The statistics of imports and exports of nuclear fuels and source materials compiled by the German Federal Office for Industry (Bundesamt fuer Wirtschaft) and the Federal Ministry for the Environment, Protection of Nature, and Reactor Safety (Bundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit) shows a 29.1% increase in imports and a 16.9% decrease of exports in 1987 compared to the previous year. A major rise was experienced in imports of natural uranium, uranium enriched up to 3% and to 3-10%, and plutonium, while there was a decline in imports of depleted uranium, source materials, and more highly enriched uranium. Uranium enriched 3-10%, highly enriched uranium, and plutonium were exported in larger quantities, while only smaller quantities of depleted uranium, source materials, natural uranium, uranium enriched up to 3%, and uranium enriched 10-85% were exported. (orig.) [de

  3. Upgrading safety documentation for exported nuclear power plants

    International Nuclear Information System (INIS)

    Rosen, M.

    1978-01-01

    In view of the generally small regulatory staffs of importing countries, suggestions are given for upgrading the ''export edition'' of the traditionally supplied safety documentation by use of a Supplementary Information Report, written specifically for the needs of a smaller and/or less technically qualified staff, which would highlight the differences that exist between the facility to be constructed and the supposedly similar reference plant of the supplier country; by improvement of supporting safety documentation to allow for adequate understanding of significant safety parameters; and by attention to the needs of smaller countries in the critical operating regulations (Technical Specifications for Operation). (author)

  4. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.

    Science.gov (United States)

    Bedard, James E J; Purnell, Jennifer D; Ware, Stephanie M

    2007-01-15

    Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

  5. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    Science.gov (United States)

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-10-01

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  6. Nuclear export controls and the CTBT: Where we've been and challenges ahead - Views of an engineer

    International Nuclear Information System (INIS)

    Lundy, A.S.

    1998-01-01

    The paper discusses the following topics: the importance of export controls; the uniqueness of nuclear weapons and their export control requirements; ''dual-use'' controls; and recent developments in nonproliferation beyond export control. Also discussed are some non-obvious challenges which include computer modeling and visualization, and fissile material availability and instant nukes. The author concludes by asking the Nuclear Suppliers Group to consider whether there are ways to make its controls more effective

  7. Nuclear export controls and the CTBT: Where we`ve been and challenges ahead -- Views of an engineer

    Energy Technology Data Exchange (ETDEWEB)

    Lundy, A.S.

    1998-09-01

    The paper discusses the following topics: the importance of export controls; the uniqueness of nuclear weapons and their export control requirements; ``dual-use`` controls; and recent developments in nonproliferation beyond export control. Also discussed are some non-obvious challenges which include computer modeling and visualization, and fissile material availability and instant nukes. The author concludes by asking the Nuclear Suppliers Group to consider whether there are ways to make its controls more effective.

  8. Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress.

    Science.gov (United States)

    Shaheen, Alaa

    2018-05-05

    The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

  9. Nuclear Sanctions: Section 102(b) of the Arms Export Control Act and its Application to India and Pakistan

    National Research Council Canada - National Science Library

    Grimmett, Jeanne J

    2001-01-01

    Section 102(b) of the Arms Export Control Act (AECA) requires the President to impose sanctions on any country that he has determined is a "non-nuclear-weapon state" and has received or detonated a "nuclear explosive device...

  10. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received notes verbales dated 27 August 1993 and 28 October 1993 from the Permanent Missions of Finland and Spain to the International Atomic Energy relating to the export of nuclear material, equipment and technology. The purpose of these notes verbales is to provide further information on those Governments' nuclear export policies and practices

  11. Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer

    DEFF Research Database (Denmark)

    Chen, Ying; Camacho, Sandra Catalina; Silvers, Thomas R

    2017-01-01

    Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluate...

  12. Problems associated with the export of nuclear power plants

    International Nuclear Information System (INIS)

    Rosen, M.

    1978-01-01

    The symposium was attended by 130 participants from 31 countries and 3 international organizations. The symposium gave special emphasis to the problems facing developing countries in the initial stages of nuclear power programmes, and was divided into three major topics: nuclear safety, domestic contributions, and international aspects. Thirty-seven papers were presented in nine sessions

  13. Research on export system of marine nuclear power device

    International Nuclear Information System (INIS)

    Fu Mingyu; Bian Xinqian; Shi Ji; Xin Chengdong; Wei Dong

    2002-01-01

    A marine nuclear power plant simulation system is founded, and a management expert system, which can administer and diagnose the typical faults, is constituted by the intelligent expert theory. This real-time expert system can analyze the reason of the typical fault caused by the nuclear power plant practically running and give the best solvent by the expert knowledge reasoning in the repository; a neural network fault inspection and diagnosis expert system which can inspect every equipment continually and give the faults diagnosis result based on the inspective dates is established. Based on the three hierarchical architecture, the operation performance is improved very much by using of the neural network fault inspection and diagnosis expert system to inspect and diagnose the nuclear power plant faults and the management expert system to supervise the nuclear power plant running. The expert system research can give guidance for the marine nuclear power plant safety operation

  14. Physical protection of export/import and transportation of nuclear material in the Slovak Republic

    International Nuclear Information System (INIS)

    Vaclav, J

    2002-01-01

    Full text: The paper contains short overview about average amount of nuclear materials transported on the territory of the Slovak Republic in a year, and the physical protection of these nuclear materials. There are several types of transportation and export/import of nuclear materials in the SR: fresh fuel import; import of other unirradiated nuclear materials (e.g. depleted uranium, natural uranium); export of unirradiated nuclear materials (e.g. natural uranium); internal transportation of fresh fuel; internal transportation of other unirradiated nuclear materials; internal transportation of spent fuel. The main objective of the nuclear regulatory authority SR is to supervise observation of the national legislation as follows: the act no. 130 / 1998 on peaceful use of nuclear energy; UJD SR's regulation no. 186/1999 which details the physical protection of the nuclear facilities, nuclear materials, and radioactive waste (following requirements of INFCIRC 225 / Rev. 4); UJD SR's regulation no. 284 / 1999 which details conditions of nuclear material and radioactive wastes transportation. (author)

  15. Examining the intersection between splicing, nuclear export and small RNA pathways.

    Science.gov (United States)

    Nabih, Amena; Sobotka, Julia A; Wu, Monica Z; Wedeles, Christopher J; Claycomb, Julie M

    2017-11-01

    Nuclear Argonaute/small RNA pathways in a variety of eukaryotic species are generally known to regulate gene expression via chromatin modulation and transcription attenuation in a process known as transcriptional gene silencing (TGS). However, recent data, including genetic screens, phylogenetic profiling, and molecular mechanistic studies, also point to a novel and emerging intersection between the splicing and nuclear export machinery with nuclear Argonaute/small RNA pathways in many organisms. In this review, we summarize the field's current understanding regarding the relationship between splicing, export and small RNA pathways, and consider the biological implications for coordinated regulation of transcripts by these pathways. We also address the importance and available approaches for understanding the RNA regulatory logic generated by the intersection of these particular pathways in the context of synthetic biology. The interactions between various eukaryotic RNA regulatory pathways, particularly splicing, nuclear export and small RNA pathways provide a type of combinatorial code that informs the identity ("self" versus "non-self") and dictates the fate of each transcript in a cell. Although the molecular mechanisms for how splicing and nuclear export impact small RNA pathways are not entirely clear at this early stage, the links between these pathways are widespread across eukaryotic phyla. The link between splicing, nuclear export, and small RNA pathways is emerging and establishes a new frontier for understanding the combinatorial logic of gene regulation across species that could someday be harnessed for therapeutic, biotechnology and agricultural applications. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  17. HCTISN: no secret export of nuclear wastes to Russia

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Recently a controversy has broken out about the EDF's exports of depleted uranium to Russia. This depleted uranium comes from 2 sources: the tailings of uranium enrichment (from EURODIF plant) and the recycling of spent fuels (from La Hague plant). Depleted uranium is sent to Russia to be enriched by centrifugation process, this enrichment generates new depleted uranium that is kept by Russia, enriched uranium is sent back to France. As it is stipulated in all enrichment contracts the company that operates the enrichment keeps the depleted material, it is the case of Tenex the Russian company. This depleted uranium can not be considered as a waste because it is stored to be used as fuel for future fast reactors. (A.C.)

  18. Export Control Guide: Loose Parts Monitoring Systems for Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Langenberg, Donald W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2012-12-01

    This report describes a typical LPMS, emphasizing its application to the RCS of a modern NPP. The report also examines the versatility of AE monitoring technology by describing several nuclear applications other than loose parts monitoring, as well as some non-nuclear applications. In addition, LPMS implementation requirements are outlined, and LPMS suppliers are identified. Finally, U.S. export controls applicable to LPMSs are discussed.

  19. Four decades of living with the genie: United States nuclear export policy

    International Nuclear Information System (INIS)

    Kramish, A.

    1983-01-01

    The subject is discussed as follows: general introduction (examples of complex nature of nuclear trade); non-proliferation policy - the beginnings (early US action to control dealings with other countries); the Nuclear Non-Proliferation Act of 1978 (formulation of US policy on nuclear trade; INFCE (International Nuclear Fuel Cycle Evaluation)); the Symington and Glenn Amendments (US legislation to control trade with other countries); the Export-Import Bank Act (US legislation for the same purpose as above); the Non-Proliferation Treaty; the Reagan Policy (US present policy to support IAEA safeguards and Non-Proliferation Treaty); future prospects. (U.K.)

  20. SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seung Kuk; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

    2016-02-05

    Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.

  1. Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

    Science.gov (United States)

    Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

    2010-03-15

    Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. A study on improvement of export control system for the nuclear facility

    International Nuclear Information System (INIS)

    Kim, Ok Joo; Shin, Dong Hoon; Yang, Seung Hyo

    2012-01-01

    The Republic of Korea joined Nuclear Suppliers Group(NSG) in 1995 and became a major nuclear supplier both in name and reality by contracting the Project of UAE Braka Nuclear Power Plant(BNPP) in 2009 and the Project of Jordan Research and Training Reactor(JRTR) in 2010. And ROK is currently negotiating with several countries such as Finland and Vietnam for more projects, so it is expected to obtain more orders of commercial and research reactor. At this point of time, we found that it is difficult to apply individual export licensing system as it is for the big nuclear project such as BNPP and JRTR Project. Because the nuclear project in foreign country contains transfer of thousands of items and technical documents, including a considerable number of strategic items, issuing individual licenses for all items and documents can cause the inefficiency of the project. So, an appropriate export control system which can support such a project is necessary. In this study, we focused on how to improve the export control system to guarantee not only time efficiency but careful management of strategic goods

  3. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    International Nuclear Information System (INIS)

    Jo, Hye-Ryeong; Kim, Yong-Seok; Son, Hyeon

    2016-01-01

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  4. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hye-Ryeong [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Kim, Yong-Seok [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of); Son, Hyeon, E-mail: hyeonson@hanyang.ac.kr [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of)

    2016-01-29

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  5. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  6. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  7. Role of Non-Government Organizations in strengthening Kazakstan nuclear export control

    International Nuclear Information System (INIS)

    Tazhibaeva, L.; Prokhodtseva, T.

    2002-01-01

    Non-governmental organizations (NGO) are the structures that were born by the time, the time when deep changes in our society led us to new trends in the all spheres of society development, to new decisions and, as a consequence, to new structural findings that where able to govern, to support and put into reality the new ideas the could not be inserted in the structure assemblies of the former society. All non-governmental organizations in Kazakhstan are younger than ten years old, but they already could be considered highly experienced, for intensity of their activity is rather high. The main advantages of NGOs are flexibility and independent source of ideas, basic data and policy assessment. There are several non-government organizations that are working in the field of non-proliferation and export control. Kazakhstan Nuclear Technology Safety Center (NTSC) is among them. Non-proliferation and export control is only a small part of activity that NTSC is involved in. Non-governmental organizations could be of several types: NGOs that are affiliated with university or institute, independent associations, quasi-governmental structures and various foundations. NTSC complementing efforts of Kazakhstan Atomic Energy Committee (KAEC) in the field of non-proliferation and export control. The activity of NTSC in the field of non-proliferation includes: Holding conferences, seminars and workshops; Creating databases and reports; Develop proposal for legislation; Provide specialized training; Analyze data. NTSC is involved in a number of projects devoted to non-proliferation and export control. The following projects are supported by the US Department of Energy cooperation program on nuclear export controls for Russia and the Newly Independent States: System to review Kazakhstan exports (STROKE); Computerization of historical licensing data; Export control reference materials for Kazakhstan organizations; Additional Protocol. STROKE is a technical analysis database for

  8. Cell biological characterization of the malaria vaccine candidate trophozoite exported protein 1.

    Directory of Open Access Journals (Sweden)

    Caroline Kulangara

    Full Text Available In a genome-wide screen for alpha-helical coiled coil motifs aiming at structurally defined vaccine candidates we identified PFF0165c. This protein is exported in the trophozoite stage and was named accordingly Trophozoite exported protein 1 (Tex1. In an extensive preclinical evaluation of its coiled coil peptides Tex1 was identified as promising novel malaria vaccine candidate providing the rational for a comprehensive cell biological characterization of Tex1. Antibodies generated against an intrinsically unstructured N-terminal region of Tex1 and against a coiled coil domain were used to investigate cytological localization, solubility and expression profile. Co-localization experiments revealed that Tex1 is exported across the parasitophorous vacuole membrane and located to Maurer's clefts. Change in location is accompanied by a change in solubility: from a soluble state within the parasite to a membrane-associated state after export to Maurer's clefts. No classical export motifs such as PEXEL, signal sequence/anchor or transmembrane domain was identified for Tex1.

  9. RNA Export through the NPC in Eukaryotes.

    Science.gov (United States)

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  10. Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus.

    Science.gov (United States)

    Wolfisberg, Raphael; Kempf, Christoph; Ros, Carlos

    2016-06-01

    Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process. In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid

  11. Tap and Dbp5, but not Gag, are involved in DR-mediated nuclear export of unspliced Rous sarcoma virus RNA

    International Nuclear Information System (INIS)

    LeBlanc, Jason J.; Uddowla, Sabena; Abraham, Benjamin; Clatterbuck, Sarah; Beemon, Karen L.

    2007-01-01

    All retroviruses must circumvent cellular restrictions on the export of unspliced RNAs from the nucleus. While the unspliced RNA export pathways for HIV and Mason-Pfizer monkey virus are well characterized, that of Rous sarcoma virus (RSV) is not. We have previously reported that the RSV direct repeat (DR) elements are involved in the cytoplasmic accumulation of unspliced viral RNA. Here, using fluorescent in situ hybridization (FISH), we demonstrate that unspliced viral RNAs bearing a single point mutation (G8863C) in the DR exhibit a restricted cellular localization in and around the nucleus. In contrast, wild type unspliced viral RNA had a diffuse localization throughout the nucleus and cytoplasm. Since the RSV Gag protein has a transient localization in the nucleus, we examined the effect of Gag over-expression on a DR-mediated reporter construct. While Gag did not enhance DR-mediated nuclear export, the dominant-negative expression of two cellular export factors, Tap and Dbp5, inhibited expression of the same reporter construct. Furthermore, FISH studies using the dominant-negative Dbp5 demonstrated that unspliced wild type RSV RNA was retained within the nucleus. Taken together, these results further implicate the DR in nuclear RNA export through interactions with Tap and Dbp5

  12. U.S. nuclear non-proliferation policy: impact on exports and nuclear industry could not be determined. Report to the Congress

    International Nuclear Information System (INIS)

    1980-01-01

    The Nuclear Non-Proliferation Act of 1978 established new measures to prevent the diversion to weapons use of peaceful nuclear exports. It also created a policy to confirm U.S. reliability as a nuclear supplier. GAO did not identify any export sales lost as a result of the Act, but did find indications that nonproliferation policies can influence export sales. Based on available data, GAO could not determine the impact of the Act on the competitiveness of U.S. nuclear exports. However, U.S. companies are at some disadvantage because importers perceive that implementation of the Act may result in delayed export licenses. The United States dominated the nuclear export market through the early 1970s. However, foreign competitors, some aided by U.S. technology transfers, emerged to monopolize home markets and compete for third-country business. Further, the market has been depressed since 1974 and prospects for U.S. nuclear power plant exports have dimmed greatly. However, U.S. companies continue to view exports as important to sustain production capacity

  13. Notification to the Agency of exports and imports of nuclear material

    International Nuclear Information System (INIS)

    1991-12-01

    The document reproduces the letter dated 15 November 1991 received by the Director General of the IAEA from the Resident Representative to the Agency of the People's Republic of China, informing him that, in the interest of assisting the Agency in its safeguards activities, the Government of the People's Republic of China had decided to provide it henceforth with information on exports and imports of nuclear material

  14. Notification to the Agency of Exports and Imports of Nuclear Material

    International Nuclear Information System (INIS)

    1984-03-01

    On 16 February 1984 the Director General received a letter dated 7 February 1984 from the Governor from France on the Agency's Board of Governors informing him that, in the interest of assisting the Agency in its safeguards activities, the Government of France had decided to provide it henceforth with information on exports and imports of nuclear material. In the light of the request made in this letter, its text is reproduced

  15. Notification to the Agency of Exports and Imports of Nuclear Material

    International Nuclear Information System (INIS)

    1974-01-01

    On 11 July 1974 the Director General received letters dated 10 July from the Resident Representatives to the Agency of the Union of Soviet Socialist Republics, the United Kingdom of Great Britain and Northern Ireland and the United States of America informing him that in the interest of assisting the Agency in its safeguards activities, the Governments of these three Members had decided to provide it henceforth with information on exports and imports of nuclear material

  16. Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

    2015-01-01

    Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

  17. Nuclear exports. Parliamentary control and confidentiality; Parlamentarische Kontrolle und Geheimhaltungsbeduerftigkeit bei Nuklearexporten. Zum Urteil des Bundesverfassungsgerichts vom 21. Oktober 2014

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2015-03-15

    With its decision taken on 21. October 2014 (Az.: 2 BvE 5/11) the Federal Constitutional Court (BVerfG) decided during court proceedings between administrative bodies on the scope and limits of the parliamentary right of information. Even though the proceeding did not deal with nuclear exports but arm exports, foreign trade law, however, does not only designate an export licence obligation for military weapons but also for so called dual-use goods meaning goods, which can be used both for friendly as well as for military purposes. The export of these goods requires according to the so-called Dual-Use Regulation (EG) 428/2009 a licence. Annex I category 0 of the regulation (EG) 428/2009 lists a variety of nuclear materials, plants and equipment items for which this licence applies. In the same manner as arm exports, also exports of nuclear dual-use goods are being discussed in a special cabinet committee, the Federal Security Council (BSR), which shall coordinate cross-departmentally the German security and defence policy under consideration of economic interests and which categorises its results, according to the rules of procedure, as confidential. Also legally not regulated but common ''preliminary enquiries'' at the responsible Federal Ministry or rather Federal Office of Economics and Export Control by companies which plan an export and want to affirm the general approval for their export business prior to conclusion of contract take not only place for arm exports but also for nuclear dual-use goods. The decision by the Federal Constitutional Court can be applied to consultations about the authorisation of nuclear dual-use goods.

  18. Communication received from the Permanent Mission of New Zealand regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1995-01-01

    The Director General has received a note verbale dated 22 December 1994 from the Permanent Mission of New Zealand to the International Atomic Energy Agency providing information on the nuclear export policies and practices of the Government of New Zealand

  19. Communication Received from Argentina regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1993-10-01

    The Director General has received letters dated 27 May 1993 from the Resident Representatives of Portugal and Spain to the Agency concerning the export of nuclear material and of certain categories of equipment and other material [ru

  20. Communications received from members regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1993-05-01

    The document reproduces the letter dated 11 February 1993 from the Resident Representative of the Russian Federation to the Agency concerning the export of nuclear material and of certain categories of equipment and other material

  1. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1993-10-01

    The Director General has received letters dated 27 May 1993 from the Resident Representatives of Portugal and Spain to the Agency concerning the export of nuclear material and of certain categories of equipment and other material [es

  2. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment or technology

    International Nuclear Information System (INIS)

    1988-11-01

    The document reproduces the text of a Note Verbale dated 20 October 1988 received by the IAEA Director General from the Permanent Mission of Spain relating to the export of nuclear material, equipment or technology

  3. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment or technology

    International Nuclear Information System (INIS)

    1990-08-01

    The document reproduces the text of the Note Verbale dated 1 August 1990 received by the Director General of the IAEA from the Permanent Mission of Romania and relating to the export of nuclear material, equipment and technology

  4. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-01-01

    The document reproduces the text of the Note Verbale dated 18 December 1991 received by the Director General of the IAEA from the Permanent Mission of Austria and relating to the export of nuclear material, equipment and technology

  5. Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole.

    Directory of Open Access Journals (Sweden)

    Aurélie Fougère

    2016-11-01

    Full Text Available Many variant proteins encoded by Plasmodium-specific multigene families are exported into red blood cells (RBC. P. falciparum-specific variant proteins encoded by the var, stevor and rifin multigene families are exported onto the surface of infected red blood cells (iRBC and mediate interactions between iRBC and host cells resulting in tissue sequestration and rosetting. However, the precise function of most other Plasmodium multigene families encoding exported proteins is unknown. To understand the role of RBC-exported proteins of rodent malaria parasites (RMP we analysed the expression and cellular location by fluorescent-tagging of members of the pir, fam-a and fam-b multigene families. Furthermore, we performed phylogenetic analyses of the fam-a and fam-b multigene families, which indicate that both families have a history of functional differentiation unique to RMP. We demonstrate for all three families that expression of family members in iRBC is not mutually exclusive. Most tagged proteins were transported into the iRBC cytoplasm but not onto the iRBC plasma membrane, indicating that they are unlikely to play a direct role in iRBC-host cell interactions. Unexpectedly, most family members are also expressed during the liver stage, where they are transported into the parasitophorous vacuole. This suggests that these protein families promote parasite development in both the liver and blood, either by supporting parasite development within hepatocytes and erythrocytes and/or by manipulating the host immune response. Indeed, in the case of Fam-A, which have a steroidogenic acute regulatory-related lipid transfer (START domain, we found that several family members can transfer phosphatidylcholine in vitro. These observations indicate that these proteins may transport (host phosphatidylcholine for membrane synthesis. This is the first demonstration of a biological function of any exported variant protein family of rodent malaria parasites.

  6. Nuclear Trafficking of Retroviral RNAs and Gag Proteins during Late Steps of Replication

    Directory of Open Access Journals (Sweden)

    Matthew S. Stake

    2013-11-01

    Full Text Available Retroviruses exploit nuclear trafficking machinery at several distinct stages in their replication cycles. In this review, we will focus primarily on nucleocytoplasmic trafficking events that occur after the completion of reverse transcription and proviral integration. First, we will discuss nuclear export of unspliced viral RNA transcripts, which serves two essential roles: as the mRNA template for the translation of viral structural proteins and as the genome for encapsidation into virions. These full-length viral RNAs must overcome the cell’s quality control measures to leave the nucleus by co-opting host factors or encoding viral proteins to mediate nuclear export of unspliced viral RNAs. Next, we will summarize the most recent findings on the mechanisms of Gag nuclear trafficking and discuss potential roles for nuclear localization of Gag proteins in retrovirus replication.

  7. Export control guide: Spent nuclear fuel reprocessing and preparation of plutonium metal

    International Nuclear Information System (INIS)

    1993-10-01

    The international Treaty on the Non-Proliferation of Nuclear Weapons, also referred to as the Non-Proliferation Treaty (NPT), states in Article III, paragraph 2(b) that open-quotes Each State Party to the Treaty undertakes not to provide . . . equipment or material especially designed or prepared for the processing, use or production of special fissionable material to any non-nuclear-weapon State for peaceful purposes, unless the source or special fissionable material shall be subject to the safeguards required by this Article.close quotes This guide was prepared to assist export control officials in the interpretation, understanding, and implementation of export laws and controls relating to the international Trigger List for irradiated nuclear fuel reprocessing equipment, components, and materials. The guide also contains information related to the production of plutonium metal. Reprocessing and its place in the nuclear fuel cycle are described briefly; the standard procedure to prepare metallic plutonium is discussed; steps used to prepare Trigger List controls are cited; descriptions of controlled items are given; and special materials of construction are noted. This is followed by a comprehensive description of especially designed or prepared equipment, materials, and components of reprocessing and plutonium metal processes and includes photographs and/or pictorial representations. The nomenclature of the Trigger List has been retained in the numbered sections of this document for clarity

  8. 1988 nuclear fuel imports and exports of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    The statistic of imports and exports of nuclear fuels and source materials compiled by the Federal Office for Industry on behalf of the Federal Ministry for the Environment, Nature Conservation, and Reactor Safety show a 32.3% decrease in imports and a 17.6% increase in exports in 1988 compared to the previous year. Most of the imports are made up of source materials, natural uranium, and uranium enriched up to 10%. The term 'source material' as used in these statistics refers only to uranium concentrate. A considerable increase is reported in imports of uranium enriched 3 to 10% and of plutonium. All other products have suffered major or minor decreases. (orig.)

  9. A Study on the cooperation policy in multilateral nuclear control regimes and the advancing of national export control system

    International Nuclear Information System (INIS)

    Lee, Byung Wook; Oh, K. B.; Yang, M. H.; Lee, H. M.; Lee, K. S.; Ko, H. S.; Ryu, J. S.; Kim, J. S.

    2004-08-01

    This study carried out the analysis of trends of the multilateral nuclear control in four aspects. First, this study analyzes the past trends of the international nuclear non-proliferation regime, which includes the NPT, the IAEA safeguards system, the international nuclear export control regime and the physical protection of nuclear materials. Second, this study establishes the multilateral cooperation strategies for the effective cooperation in the process of strengthening the nuclear control regimes. Third, this study reviews the major agenda of nuclear control regimes and establishes national positions on each agenda. Fourth, this study also analyzes outstanding issues in nuclear control regimes and derives some factors to reflect national nuclear control system

  10. Effect of Appropriate Marketing Mix Strategies on Iranian Protein Products Export Performance

    OpenAIRE

    Hossein Rezaie Dolatabadi; Mohammad Hossein Forghani; Seyed Mehdi Tabatabaee; Fatemeh Faghani

    2013-01-01

    The purpose of the present paper is to examine effect of effect of appropriate marketing mix strategies on Iranian protein products export performance. 4P (Price, Product, Place, Promotion) were selected as marketing strategies. The data used to test the hypotheses were collected through an online standard questionnaire. The respondents were asked to rate on the scale between strongly agree and strongly Disagree. Reliability of questionnaire was measured using Cronbach Coefficient Alpha. The ...

  11. Interactions between mRNA export commitment, 3'-end quality control, and nuclear degradation

    DEFF Research Database (Denmark)

    Libri, Domenico; Dower, Ken; Boulay, Jocelyne

    2002-01-01

    Several aspects of eukaryotic mRNA processing are linked to transcription. In Saccharomyces cerevisiae, overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells, yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional el...... results show that several classes of defective RNPs are subject to a quality control step that impedes release from transcription site foci and suggest that suboptimal messenger ribonucleoprotein assembly leads to RNA degradation by Rrp6p....

  12. Identification of an exported heat shock protein 70 in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Grover Manish

    2013-01-01

    Full Text Available Host cell remodelling is a hallmark of malaria pathogenesis. It involves protein folding, unfolding and trafficking events and thus participation of chaperones such as Hsp70s and Hsp40s is well speculated. Until recently, only Hsp40s were thought to be the sole representative of the parasite chaperones in the exportome. However, based on the re-annotated Plasmodium falciparum genome sequence, a putative candidate for exported Hsp70 has been reported, which otherwise was known to be a pseudogene. We raised a specific antiserum against a C-terminal peptide uniquely present in PfHsp70-x. Immunoblotting and immunofluorescence-based approaches in combination with sub-cellular fractionation by saponin and streptolysin-O have been taken to determine the expression and localization of PfHsp70-x in infected erythrocyte. The re-annotated sequence of PfHsp70-x reveals it to be a functional protein with an endoplasmic reticulum signal peptide. It gets maximally expressed at the schizont stage of intra-erythrocytic life cycle. Majority of the protein localizes to the parasitophorous vacuole and some of it gets exported to the erythrocyte compartment where it associates with Maurer’s clefts. The identification of an exported parasite Hsp70 chaperone presents us with the fact that the parasite has evolved customized chaperones which might be playing crucial roles in aspects of trafficking and host cell remodelling.

  13. Protein Export by the Mycobacterial SecA2 System Is Determined by the Preprotein Mature Domain

    Science.gov (United States)

    Feltcher, Meghan E.; Gibbons, Henry S.; Ligon, Lauren S.

    2013-01-01

    At the core of the bacterial general secretion (Sec) pathway is the SecA ATPase, which powers translocation of unfolded preproteins containing Sec signal sequences through the SecYEG membrane channel. Mycobacteria have two nonredundant SecA homologs: SecA1 and SecA2. While the essential SecA1 handles “housekeeping” export, the nonessential SecA2 exports a subset of proteins and is required for Mycobacterium tuberculosis virulence. Currently, it is not understood how SecA2 contributes to Sec export in mycobacteria. In this study, we focused on identifying the features of two SecA2 substrates that target them to SecA2 for export, the Ms1704 and Ms1712 lipoproteins of the model organism Mycobacterium smegmatis. We found that the mature domains of Ms1704 and Ms1712, not the N-terminal signal sequences, confer SecA2-dependent export. We also demonstrated that the lipid modification and the extreme N terminus of the mature protein do not impart the requirement for SecA2 in export. We further showed that the Ms1704 mature domain can be efficiently exported by the twin-arginine translocation (Tat) pathway. Because the Tat system exports only folded proteins, this result implies that SecA2 substrates can fold in the cytoplasm and suggests a putative role of SecA2 in enabling export of such proteins. Thus, the mycobacterial SecA2 system may represent another way that bacteria solve the problem of exporting proteins that can fold in the cytoplasm. PMID:23204463

  14. International legal and political issues associated with the export/import of nuclear power plants

    International Nuclear Information System (INIS)

    Manning Muntzing, L.

    1978-01-01

    The benefits of nuclear power can be achieved by most nations only through international commerce that has been shaped by political considerations and implemented through legal instruments. The end product is a structure of legal agreements designed to implement the basic political and commercial decisions that are required for any nation to enter the nuclear power arena. The IAEA Statute, the Non-Proliferation Treaty and regional nuclear agreements have reflected the international political consensus concerning nuclear power. In recent years, however, events have occurred that in all probability will result in additional international arrangements. It is expected that the increase in terrorist activities will result in greater physical protection commitments, that concern for weapons proliferation will result in further definition of sanctions, and that such troublesome issues as double labelling of materials will be discussed by the international community. In areas such as bilateral agreements between nations, commercial arrangements and export licences, this is a period of rethinking, renegotiating, and readjusting. The result is a degree of uncertainty and lack of stability that could so jeopardize the potential for nuclear transfers that the nuclear energy option may not vest. While there always will be questions and issues, it is essential to settle some of the key problems without delay so that nuclear benefits can be realized. (author)

  15. France's Efforts to Promote NPP Exports and the Implications on the Role of Nuclear Regulatory Body

    International Nuclear Information System (INIS)

    Oh, Chae-Woon; Chang, Hyun-Sop; Choi, Young-Sung

    2008-01-01

    The global society facing sky-rocketing oil prices, global warming effects, and increased demand for electricity recognizes the comparative advantages of nuclear energy in terms of environmental impact and economic efficiency over the other energy sources of current use. Approximately 300 nuclear power plants (NPPs) expect to be constructed until 2030 worldwide. Accordingly, the global market size of nuclear power industry becomes scaled up to the extent of U$75 billion on the assumption that the construction of one reactor costs around U$2.5 billion. The nations in possession of advanced nuclear technology such as the U.S., France, Japan, etc not only recognized an abounding profitability in nuclear industry and anticipated nuclear renaissance but also prepared long before whatever necessary to expand their nuclear programs beyond their domestic boundaries. Amongst those nations, it seems to be France that has unfolded a remarkable array of government-led activities to export Evolutionary Pressurized Reactors (EPRs) under the cooperation of President, relevant government administration, utilities even a regulatory body. The omni-directional activities of France and its implications are presented in this paper

  16. Communications received from Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    The Director General has received notes verbales relating to the export of nuclear material, equipment and technology from the following Permanent Missions to the International Atomic Energy Agency: notes verbales dated 15 June 1994 from the Permanent Missions of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America; and a note verbale dated 10 November 1994 from the Permanent Mission of the Russian Federation. The purpose of these notes verbales is to provide further information on these Governments' nuclear export policies and practices. In the light of the wish expressed at the end of each note verbale, the analogous text of the notes verbales is attached hereto. The enclosure of these notes verbales with the amendments to the ''Guidelines for Nuclear Transfers'' contained in INFCIRC/254/Rev.1/Part 1/Mod.1 is reproduced in the Annex

  17. The Transformations of French Nuclear Export Policy (1974-1976): A Triple Double Game

    International Nuclear Information System (INIS)

    Pouponneau, Florent

    2013-01-01

    A number of problems present themselves for any scholar seeking to take into account all determinants relating to 'national' and 'international' action in the analysis of foreign policy. In the domain of the French diplomatic practices of the mid-1970's-structured around the apparent issue of nuclear exports-archival consultation and interviews reveal that the various actors involved in this policy were not necessarily playing the same national and international 'double game.' While relations between states shape what they are and do, the various effects of refraction at work at the internal level prevents one from speaking of a state taken uniformly across a space of competition

  18. CRM1-mediated nuclear export is required for 26 S proteasome-dependent degradation of the TRIP-Br2 proto-oncoprotein.

    Science.gov (United States)

    Cheong, Jit Kong; Gunaratnam, Lakshman; Hsu, Stephen I-Hong

    2008-04-25

    Overexpression of the proto-oncogene TRIP-Br2 (SERTAD2) has been shown to induce E2F activity and promote tumorigenesis, whereas ablation of TRIP-Br2 arrests cell proliferation. Timely degradation of many cell cycle regulators is fundamental to the maintenance of proper cell cycle progression. Here we report novel mechanism(s) that govern the tight regulation of TRIP-Br2 levels during cell cycle progression. TRIP-Br2 was observed to be a short-lived protein in which the expression level peaks at the G(1)/S boundary. TRIP-Br2 accumulated in cells treated with 26 S proteasome inhibitors. Co-immunoprecipitation studies revealed that TRIP-Br2 forms ubiquitin conjugates. In silico analysis identified a putative leucine-rich nuclear export signal (NES) motif that overlaps with the PHD-Bromo interaction domain in the acidic C-terminal transactivation domain (TAD) of TRIP-Br2. This NES motif is highly conserved in widely divergent species and in all TRIP-Br family members. TRIP-Br2 was shown to be stabilized in G(2)/M phase cells through nuclear entrapment, either by deletion of the acidic C-terminal TAD, which includes the NES motif, or by leptomycin B-mediated inhibition of the CRM1-dependent nuclear export machinery. Mutation of leucine residue 238 of this NES motif abolished the interaction between CRM1 and TRIP-Br2, as well as the nuclear export of TRIP-Br2 and its subsequent 26 S proteasome-dependent degradation. These data suggest that CRM1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of TRIP-Br2.

  19. A peptide export-import control circuit modulating bacterial development regulates protein phosphatases of the phosphorelay.

    Science.gov (United States)

    Perego, M

    1997-08-05

    The phosphorelay signal transduction system activates developmental transcription in sporulation of Bacillus subtilis by phosphorylation of aspartyl residues of the Spo0F and Spo0A response regulators. The phosphorylation level of these response regulators is determined by the opposing activities of protein kinases and protein aspartate phosphatases that interpret positive and negative signals for development in a signal integration circuit. The RapA protein aspartate phosphatase of the phosphorelay is regulated by a peptide that directly inhibits its activity. This peptide is proteolytically processed from an inactive pre-inhibitor protein encoded in the phrA gene. The pre-inhibitor is cleaved by the protein export apparatus to a putative pro-inhibitor that is further processed to the active inhibitor peptide and internalized by the oligopeptide permease. This export-import circuit is postulated to be a mechanism for timing phosphatase activity where the processing enzymes regulate the rate of formation of the active inhibitor. The processing events may, in turn, be controlled by a regulatory hierarchy. Chromosome sequencing has revealed several other phosphatase-prepeptide gene pairs in B. subtilis, suggesting that the use of this mechanism may be widespread in signal transduction.

  20. Communications received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-04-01

    The document reproduces the Note Verbale dated 8 February 1993 received by the Director General from the Permanent Mission of the Russian Federation to the International Organizations in Vienna, relating to the export of nuclear material, equipment or technology, in order to provide information on that Government's Guidelines for Nuclear Transfer

  1. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-01-01

    The document reproduces the Note Verbale dated 2 December 1992 received by the Director General from the Resident Representative of Argentina to the Agency relating to the export of nuclear material, equipment and technology in order to clarify parts of the Trigger List which is incorporated in Annex A to the Guidelines for Nuclear Transfers

  2. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-01-01

    The document reproduces the Note Verbale dated 2 December 1992 received by the Director General from the Resident Representative of Argentina to the Agency relating to the export of nuclear material, equipment or technology, in order to provide information on that Government's Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology

  3. HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP

    Science.gov (United States)

    Noh, Ji Heon; Kim, Kyoung Mi; Abdelmohsen, Kotb; Yoon, Je-Hyun; Panda, Amaresh C.; Munk, Rachel; Kim, Jiyoung; Curtis, Jessica; Moad, Christopher A.; Wohler, Christina M.; Indig, Fred E.; de Paula, Wilson; Dudekula, Dawood B.; De, Supriyo; Piao, Yulan; Yang, Xiaoling; Martindale, Jennifer L.; de Cabo, Rafael; Gorospe, Myriam

    2016-01-01

    Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria are poorly characterized. Using affinity RNA pull-down followed by mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich RNA sequence-binding factor 1), that associated with the nuclear DNA-encoded lncRNA RMRP and mobilized it to mitochondria. In cultured human cells, HuR bound RMRP in the nucleus and mediated its CRM1 (chromosome region maintenance 1)-dependent export to the cytosol. After RMRP was imported into mitochondria, GRSF1 bound RMRP and increased its abundance in the matrix. Loss of GRSF1 lowered the mitochondrial levels of RMRP, in turn suppressing oxygen consumption rates and modestly reducing mitochondrial DNA replication priming. Our findings indicate that RBPs HuR and GRSF1 govern the cytoplasmic and mitochondrial localization of the lncRNA RMRP, which is encoded by nuclear DNA but has key functions in mitochondria. PMID:27198227

  4. Postage for the messenger: Designating routes for Nuclear mRNA Export

    Science.gov (United States)

    Natalizio, Barbara J.; Wente, Susan R.

    2013-01-01

    Transcription of messenger(m) RNA occurs in the nucleus, making the translocation of mRNA across the nuclear envelope (NE) boundary a critical determinant of proper gene expression and cell survival. A major mRNA export route occurs via the NXF1-dependent pathway through the nuclear pore complexes (NPCs) embedded in the NE. However, recent findings have discovered new evidence supporting the existence of multiple mechanisms for crossing the NE, including both NPC-mediated and NE budding-mediated pathways. An analysis of the trans-acting factors and cis components that define these pathways reveals shared elements as well as mechanistic differences. We review here the current understanding of the mechanisms that characterize each pathway and highlight the determinants that influence mRNA transport fate. PMID:23583578

  5. Analysis of World Nuclear Market and Strategy of Korean NPP's Competitiveness Improvement for Exportation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Young; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of); Roh, Seungkook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Chang, Soon Heung [Handong Global University, Pohang (Korea, Republic of)

    2016-10-15

    China, India and USA (nuclear adopted countries) are planning tremendous number of NPPs to meet their increasing electricity demand and Saudi Arabia, Vietnam (nuclear adopting countries) are also planning to include nuclear power in their energy mix as a long-term plan. Korea has exported 4 units of APR1400 to the UAE in December, 2009. Korea became sixth NPP supplier country and our economic feasibility and safety features were started to evaluate worldwide. Nuclear industries became a new driver of Korea’s export and nuclear industries in Korea are now expecting another NPP export to Middle-eastern countries, including UAE and Saudi Arabia, based on the first-mover’s advantage at the UAE. In 2000s, five countries (Japan, USA, France, Russia and Korea), which are able to build NPP, focused on NPP export more than domestic construction. Global trend of world nuclear market changed rapidly, especially after NPP export to the UAE. By the global trend, hegemony of nuclear market migrated from supplier country to buyer country. Nuclear companies started cooperating rather than competing. Financing to developing countries become more important. In general, one of the considerable combinations is Korea-Japan-USA alliance. Korea is in charge of EPC, Japan supports financing and deficient technology (with USA partner), and Japan-USA handles fuel supply and back-end fuel cycle based on new agreed terms of ROK-US Nuclear Cooperation Agreement. This combination was judged to best way to collaborate with global companies. Paying attention to many delayed (or potentially delayed) constructions from Russia, intercepting the construction work will be available in case of contracted countries. Korea can emphasize the short construction time, high responsiveness and mild/equal diplomatic position to the target countries.

  6. Communication received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear transfers

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex

  7. Communication received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear transfers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex.

  8. Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

    Science.gov (United States)

    Hayashi, Ken'ichiro; Morita, Tsuyoshi

    2013-01-01

    Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

  9. Identification of the nuclear export signals that regulate the intracellular localization of the mouse CMP-sialic acid synthetase

    International Nuclear Information System (INIS)

    Fujita, Akiko; Sato, Chihiro; Kitajima, Ken.

    2007-01-01

    The CMP-sialic acid synthetase (CSS) catalyzes the activation of sialic acid (Sia) to CMP-Sia which is a donor substrate of sialyltransferases. The vertebrate CSSs are usually localized in nucleus due to the nuclear localization signal (NLS) on the molecule. In this study, we first point out that a small, but significant population of the mouse CMP-sialic acid synthetase (mCSS) is also present in cytoplasm, though mostly in nucleus. As a mechanism for the localization in cytoplasm, we first identified two nuclear export signals (NESs) in mCSS, based on the localization studies of the potential NES-deleted mCSS mutants as well as the potential NES-tagged eGFP proteins. These two NESs are conserved among mammalian and fish CSSs, but not present in the bacterial or insect CSS. These results suggest that the intracellular localization of vertebrate CSSs is regulated by not only the NLS, but also the NES sequences

  10. Intersectin goes nuclear: secret life of an endocytic protein.

    Science.gov (United States)

    Alvisi, Gualtiero; Paolini, Lucia; Contarini, Andrea; Zambarda, Chiara; Di Antonio, Veronica; Colosini, Antonella; Mercandelli, Nicole; Timmoneri, Martina; Palù, Giorgio; Caimi, Luigi; Ricotta, Doris; Radeghieri, Annalisa

    2018-04-27

    Intersectin 1-short (ITSN1-s) is a 1220 amino acid ubiquitously expressed scaffold protein presenting a multidomain structure that allows to spatiotemporally regulate the functional interaction of a plethora of proteins. Besides its well-established role in endocytosis, ITSN1-s is involved in the regulation of cell signaling and is implicated in tumorigenesis processes, although the signaling pathways involved are still poorly understood. Here, we identify ITSN1-s as a nucleocytoplasmic trafficking protein. We show that, by binding to importin (IMP)α, a small fraction of ITSN1-s localizes in the cell nucleus at the steady state, where it preferentially associates with the nuclear envelope and interacts with lamin A/C. However, upon pharmacological ablation of chromosome region maintenance 1 (CRM-1)-dependent nuclear export pathway, the protein accumulates into the nucleus, thus revealing its moonlighting nature. Analysis of deletion mutants revealed that the coiled coil (CC) and Src homology (SH3) regions play the major role in its nucleocytoplasmic shuttling. While no evidence of nuclear localization signal (NLS) was detected in the CC region, a functional bipartite NLS was identified within the SH3D region of ITSN1-s (RKKNPGGWWEGELQARGKKRQIGW-1127), capable of conferring energy-dependent nuclear accumulation to reporter proteins and whose mutational ablation affects nuclear import of the whole SH3 region. Thus, ITSN1-s is an endocytic protein, which shuttles between the nucleus and the cytoplasm in a CRM-1- and IMPα-dependent fashion. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  12. On The Export Control Of High Speed Imaging For Nuclear Weapons Applications

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Scott Avery [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Altherr, Michael Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-15

    Since the Manhattan Project, the use of high-speed photography, and its cousins flash radiography1 and schieleren photography have been a technological proliferation concern. Indeed, like the supercomputer, the development of high-speed photography as we now know it essentially grew out of the nuclear weapons program at Los Alamos2,3,4. Naturally, during the course of the last 75 years the technology associated with computers and cameras has been export controlled by the United States and others to prevent both proliferation among non-P5-nations and technological parity among potential adversaries among P5 nations. Here we revisit these issues as they relate to high-speed photographic technologies and make recommendations about how future restrictions, if any, should be guided.

  13. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1993-05-01

    On 13 December 1990 the Director General received a letter dated 10 December 1990 from the Resident Representative of Austria to the Agency in the same terms as the letter and its Annex reproduced in document INFCIRC/209/Rev.1. That document deals with communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material [ru

  14. Communication from the Permanent Mission of Israel to the International Atomic Energy Agency regarding nuclear export controls

    International Nuclear Information System (INIS)

    2004-01-01

    The Director General of the International Atomic Energy Agency has received a letter dated 13 July 2004 from the Permanent Mission of Israel providing information on Israel's nuclear export policies and practices. As requested by the Permanent Mission, the letter and document attached to it are reproduced herein for the information of Member States

  15. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1993-06-01

    On 13 December 1990 the Director General received a letter dated 10 December 1990 from the Resident Representative of Austria to the Agency in the same terms as the letter and its Annex reproduced in document INFCIRC/209/Rev.1. That document deals with communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material [es

  16. Communication received from Argentina regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received a letter of 27 June 1995 from the Resident Representative of Argentina to the Agency concerning the export of nuclear material and of certain categories of equipment and other material. In the light of the wish expressed at the end of the letter, the text of the letter is attached hereto

  17. A prototype system dynamic model of nuclear and radiological export controls in Central Asia and the Caucasus; enhancing the effectiveness of preventing illicit nuclear material trafficking

    International Nuclear Information System (INIS)

    Ferguston, C.D.; Ouagrham, S.B.

    2002-01-01

    An urgent need calls out for improved border security and export control systems in the Central Asian and Caucasus regions to prevent illicit nuclear and radioactive materials trafficking. Effective nuclear and radiological exports controls are essential because these regions contain numerous nuclear facilities and radioactive materials as well as lie at the crossroads between seekers and suppliers of technologies that could be employed in nuclear and radiological weapons. Porous and unprotected borders compound these concerns. Moreover, the states within these regions are struggling with forming new regulations and laws, obtaining sufficient portal monitoring equipment, training customs and border security personnel, and coordinating these activities with neighboring states. Building this infrastructure all at once can severely task any government. Thus, unsurprisingly, most of these states have inadequate export control and border security systems. To enable each state in these regions determine how to better prevent illicit nuclear and radiological materials trafficking, the authors have developed a prototype system dynamics model focused on evaluating and improving of effectiveness of export controls. System dynamics modeling, a management tool that grew out of the field of system engineering and nonlinear dynamics, uses two structures: causal loop diagrams and stock and flow diagrams. The former shows how endogenous systematic factors interact with each other to produce feedback mechanisms that results in either balancing or reinforcing loops. A classic example is a arms race, modeled as a vicious cycle or reinforcing loop. In addition to interacting with each other, causal loops influence the flow of stock, which is material concern. In the export control system dynamics model, the stock represents nuclear and radioactive materials. System dynamics modelling is an iterative process that is continually modified by user input. Therefore, export control

  18. NESbase version 1.0: a database of nuclear export signals

    DEFF Research Database (Denmark)

    la Cour, T.; Gupta, Ramneek; Rapacki, Krzysztof

    2003-01-01

    information of whether NES was shown to be necessary and/or sufficient for export, and whether the export was shown to be mediated by the export receptor CRM1. The compiled information was used to make a sequence logo of the Leucine-rich NESs, displaying the conservation of amino acids within a window of 25...

  19. Simplification of the Provisions of the Nuclear Energy Act on Imports and Exports; A Working Group Report

    International Nuclear Information System (INIS)

    2001-01-01

    The Ministry of Trade and Industry appointed a working group to map out possibilities of simplifying the provisions on imports and exports of nuclear products and to submit a proposal for the amendment of the Nuclear Energy Act in this respect. The working group should especially map out relevant international and EU norms and consider to what extent it would be possible to replace the present licensing procedure with obligations imposed on operators and/or a notification procedure. The working group should further study the possibility of combining the provisions on the control of nuclear materials, the safety of transports of nuclear and other radioactive material nuclear liability and physical protection of nuclear materials with the provisions on imports and exports. The working group did not discuss the provisions on the imports and exports of nuclear waste. The Council Regulation concerning the control of exports of dual-use items and technology, which entered into force in September 2000, and the amendment of the Regulation with a view to nuclear material adopted in January 2001 call for an amendment of the provisions of the Nuclear Energy Act concerning exports. The working group proposes that a direct reference to the EU Regulation should be included in the Nuclear Energy Decree. The definition of exports is proposed to be changed so that it corresponds to the definition in the EU Regulation. The Nuclear Energy Decree should, however, comprise provisions on applying for an authorization, on a licensing authority and on the possibility of applying for a global authorisation. The global authorisation shall replace the Intra-Community trade licence, which is proposed to be abolished. It is proposed that the Ministry of Trade and Industry should be the licensing authority. It is further proposed that provisions should be issued on a notification procedure for products falling under the scope of the Nuclear Energy Act for which no export authorisation is

  20. A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly.

    Science.gov (United States)

    Lee, C H; Chang, S C; Wu, C H; Chang, M F

    2001-03-16

    Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus, as it requires hepatitis B virus for virion production and transmission. We have previously demonstrated that sequences within the C-terminal 19-amino acid domain flanking the isoprenylation motif of the large hepatitis delta antigen (HDAg-L) are important for virion assembly. In this study, site-directed mutagenesis and immunofluorescence staining demonstrated that in the absence of hepatitis B virus surface antigen (HBsAg), the wild-type HDAg-L was localized in the nuclei of transfected COS7 cells. Nevertheless, in the presence of HBsAg, the HDAg-L became both nuclei- and cytoplasm-distributed in about half of the cells. An HDAg-L mutant with a substitution of Pro-205 to alanine could neither form HDV-like particles nor shift the subcellular localization in the presence of HBsAg. In addition, nuclear trafficking of HDAg-L in heterokaryons indicated that HDAg-L is a nucleocytoplasmic shuttling protein. A proline-rich HDAg peptide spanning amino acid residues 198 to 210, designated NES(HDAg-L), can function as a nuclear export signal (NES) in Xenopus oocytes. Pro-205 is critical for the NES function. Furthermore, assembly of HDV is insensitive to leptomycin B, indicating that the NES(HDAg-L) directs nuclear export of HDAg-L to the cytoplasm via a chromosome region maintenance 1-independent pathway.

  1. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression.

    Science.gov (United States)

    Bougdour, Alexandre; Durandau, Eric; Brenier-Pinchart, Marie-Pierre; Ortet, Philippe; Barakat, Mohamed; Kieffer, Sylvie; Curt-Varesano, Aurélie; Curt-Bertini, Rose-Laurence; Bastien, Olivier; Coute, Yohann; Pelloux, Hervé; Hakimi, Mohamed-Ali

    2013-04-17

    After invading host cells, Toxoplasma gondii multiplies within a parasitophorous vacuole (PV) that is maintained by parasite proteins secreted from organelles called dense granules. Most dense granule proteins remain within the PV, and few are known to access the host cell cytosol. We identify GRA16 as a dense granule protein that is exported through the PV membrane and reaches the host cell nucleus, where it positively modulates genes involved in cell-cycle progression and the p53 tumor suppressor pathway. GRA16 binds two host enzymes, the deubiquitinase HAUSP and PP2A phosphatase, which exert several functions, including regulation of p53 and the cell cycle. GRA16 alters p53 levels in a HAUSP-dependent manner and induces nuclear translocation of the PP2A holoenzyme. Additionally, certain GRA16-deficient strains exhibit attenuated virulence, indicating the importance of these host alterations in pathogenesis. Therefore, GRA16 represents a potentially emerging subfamily of exported dense granule proteins that modulate host function. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The function of yeast CAP family proteins in lipid export, mating, and pathogen defense.

    Science.gov (United States)

    Darwiche, Rabih; El Atab, Ola; Cottier, Stéphanie; Schneiter, Roger

    2018-04-01

    In their natural habitat, yeast cells are constantly challenged by changing environmental conditions and a fierce competition for limiting resources. To thrive under such conditions, cells need to adapt and divide quickly, and be able to neutralize the toxic compounds secreted by their neighbors. Proteins like the pathogen-related yeast, Pry proteins, which belong to the large CAP/SCP/TAPS superfamily, may have an important role in this function. CAP proteins are conserved from yeast to man and are characterized by a unique αβα sandwich fold. They are mostly secreted glycoproteins and have been implicated in many different physiological processes including pathogen defense, virulence, venom toxicity, and sperm maturation. Yeast members of this family bind and export sterols as well as fatty acids, and they render cells resistant to eugenol, an antimicrobial compound present in clove oil. CAP family members might thus exert their various physiological functions through binding, sequestration, and neutralization of such small hydrophobic compounds. © 2017 Federation of European Biochemical Societies.

  3. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    Science.gov (United States)

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2)

    NARCIS (Netherlands)

    Seitz, S.; Kretz-Rommel, A.; Oude Elferink, R. P.; Boelsterli, U. A.

    1998-01-01

    Previous work demonstrates that the reactive acyl glucuronide of the nonsteroidal antiinflammatory drug diclofenac forms selective protein adducts in the liver, which may play a causal role in the pathogenesis of diclofenac-associated liver toxicity. Because glucuronide conjugates can be exported

  5. Mapping the nuclear localization signal in the matrix protein of potato yellow dwarf virus.

    Science.gov (United States)

    Anderson, Gavin; Jang, Chanyong; Wang, Renyuan; Goodin, Michael

    2018-05-01

    The ability of the matrix (M) protein of potato yellow dwarf virus (PYDV) to remodel nuclear membranes is controlled by a di-leucine motif located at residues 223 and 224 of its primary structure. This function can be uncoupled from that of its nuclear localization signal (NLS), which is controlled primarily by lysine and arginine residues immediately downstream of the LL motif. In planta localization of green fluorescent protein fusions, bimolecular fluorescence complementation assays with nuclear import receptor importin-α1 and yeast-based nuclear import assays provided three independent experimental approaches to validate the authenticity of the M-NLS. The carboxy terminus of M is predicted to contain a nuclear export signal, which is belived to be functional, given the ability of M to bind the Arabidopsis nuclear export receptor 1 (XPO1). The nuclear shuttle activity of M has implications for the cell-to-cell movement of PYDV nucleocapsids, based upon its interaction with the N and Y proteins.

  6. A study on the establishment of national nuclear foreign policy with reference to nuclear export control system, strategy toward IAEA, and NPT review conferences

    International Nuclear Information System (INIS)

    Choi, Young Myung; Nam, Jang Soo; Lee, Han Myung

    1990-02-01

    The objectives of this study are follows: suggestion for i) our future nuclear development directions, ii) establishment of national export control system, iii) establishment of strategy toward IAEA, and suggestion of our standpoints toward the 4th NPT review conference. This study proposes the following; 1) It is desirable that nuclear power generation strategy is propelled under the premise of economics and proven technology. And international cooperation in connection with the nuclear fuel cycle should be reinforced. 2) It is recommened that nuclear export control system should be government-led. 3) Our country needs to make efforts in increasing the number of Korean staff in the IAEA, and to establish permanent mission which is wholly responsible for the IAEA affairs, and to construct a system which deals with nuclear foregin activities. 4) It is desirable that the basic position of our country toward the 4th NPT review conference should be : i) to urge parties to the NPT to conclude safeguards agreement with IAEA as early as possible, ii) to request nuclear suppliers to mitigate their nuclear technology for peaceful uses to nuclear developing countries, and iii) to urge nuclear weapon states to make further efforts for nuclear disarmament. (author)

  7. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.

    LENUS (Irish Health Repository)

    Gu, Lili

    2011-01-01

    The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.

  8. Communication from the Permanent Mission of Finland to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of Finland providing information on the export policies and practices of the Government of Finland with respect to the export of nuclear material, equipment and technology

  9. Communication from the Permanent Mission of Australia to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of Australia providing information on the export policies and practices of the Government of Australia with respect to the export of nuclear material, equipment and technology

  10. NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

    Science.gov (United States)

    Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

    2010-11-01

    Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

  11. Strategic plan for the development of core technologies for the Korean advanced nuclear power reactor for export

    International Nuclear Information System (INIS)

    Moon, Joo Hyun; Cho, Young Ho

    2010-01-01

    With the soaring oil price and worsening global warming, nuclear power has attracted considerable attention on a global scale and a new large market of nuclear power plants (NPPs) is expected. The Korean government aims to export up to 10 NPPs by 2012, based on the successful export of 2 NPPs to the UAE in 2009. It is also going to develop a follow-up model of the Advanced Power Reactor (APR) 1400, and join the world's NPP market under the banner of Korea's original reactor type. For this, it promulgated the strategic plan, NuTech 2012, a technology development plan intended for the early acquisition of core technologies for the Korean advanced NPP design and domestic production of the main components in NPP. This paper introduces the strategic plan of NuTech 2012. (orig.)

  12. Export regulation

    International Nuclear Information System (INIS)

    Gates, D.J.

    1978-01-01

    Australia is a major uranium supplier. Uranium is exported under conditions laid down to avoid any nuclear proliferation. On 24 May 1977 the Prime Minister had stated the main elements of Australian policy: the strengthening of the system of international safeguards and the selection of importing countries. (Non-nuclear weapon states must be Contracting Parties to the NPT. Nuclear weapon states must undertake not to use Australian uranium for this purpose). Australia retains property of the uranium up to the UF 6 stage (uranium hexafluoride) in the fuel cycle; it reserves the right to stop any export if the importing country no longer complies with AIEA Safeguards. Any transfer to a third country, any irradiated fuel reprocessing, requires Australia's prior agreement. Finally, importing countries must satisfy physical protection conditions. (NEA) [fr

  13. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 31 August 2001, from the Resident Representatives to the Agency of Argentina, Austria, Belarus, Belgium, Brazil, Bulgaria, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Luxembourg, Netherlands, New Zealand, Portugal, Republic of Korea, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United States and the United Kingdom, relating to the export of nuclear material, equipment and technology

  14. Communication Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment or Technology

    International Nuclear Information System (INIS)

    1978-02-01

    The Permanent Mission of ...... presents its compliments to the Director General of the International Atomic Energy Agency and has the honour to enclose copies of three documents which have been the subject of discussion between the Government of ....... and a number of other Governments. The Government of ........ has decided that, when considering the export of nuclear material, equipment or technology, it will act in accordance with the principles contained in the attached documents

  15. RanGTP-mediated nuclear export of karyopherin α involves its interaction with the nucleoporin Nup153

    OpenAIRE

    Moroianu, Junona; Blobel, Günter; Radu, Aurelian

    1997-01-01

    Using binding assays, we discovered an interaction between karyopherin α2 and the nucleoporin Nup153 and mapped their interacting domains. We also isolated a 15-kDa tryptic fragment of karyopherin β1, termed β1*, that contains a determinant for binding to the peptide repeat containing nucleoporin Nup98. In an in vitro assay in which export of endogenous nuclear karyopherin α from nuclei of digitonin-permeabilized cells was quantitatively monitored by indirect immunofluorescence with anti-kary...

  16. Safety-reductions in cut-price nuclear power plant for export

    International Nuclear Information System (INIS)

    1985-01-01

    The report concentrates on insufficiencies and defects in safety engineering in the KWU pressurised water reactor of the 1000 MW category, which is made for export. The study was carried out in the light of the impending export of such a PWR to Egypt, but it could be applied to other potential buyer countries in many aspects. (orig.) [de

  17. Communication of 15 November 2001 Received from the People's Republic of China regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General has received a letter of 15 November 2001 from the Resident Representative of the People's Republic of China concerning the export of nuclear material and of certain categories of equipment and other material

  18. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-15

    The document reproduces the text of the Notes Verbales dated 1 February 2000 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Brazil, Canada, the Czech Republic, Germany, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Switzerland, Ukraine, the United Kingdom and the United States relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. The attachment to these Notes Verbales is also included.

  19. Communications received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-07-01

    The document reproduces the text of the notes verbales dated 1 June 1992, received by the Director General from the Resident Representatives to the Agency of Australia, Austria, Belgium, Bulgaria, Canada, Czech and Slovak Federal Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment for technology. The purpose of these notes verbales is to clarify parts of the Trigger List incorporated in the Annex A to the Guidelines for Nuclear Transfer. 1 tab

  20. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Notes Verbales dated 1 February 2000 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Brazil, Canada, the Czech Republic, Germany, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Switzerland, Ukraine, the United Kingdom and the United States relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. The attachment to these Notes Verbales is also included

  1. Communication received from the permanent mission of the Argentine Republic regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    On 11 May 1994, the Director General received a note verbale from the Permanent Mission of Argentina to the International Atomic Energy Agency relating to the export of nuclear material, equipment and technology. The purpose of this note verbale is to provide further information on the nuclear export policies and practices of the Government of the Argentine Republic. In the light of the wish expressed at the end of the note verbale, the text of the note verbale is annexed hereto

  2. Communication received from the permanent mission of the Argentine Republic regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    On 11 May 1994, the Director General received a note verbale from the Permanent Mission of Argentina to the International Atomic Energy Agency relating to the export of nuclear material, equipment and technology. The purpose of this note verbale is to provide further information on nuclear export policies and practices of the Government of the Argentine Republic. In the light of the wish expressed at the end of the note verbale, the text of the note verbale is annexed hereto

  3. The Role of Export Credit Agencies in the Financing of Nuclear Power Projects. Appendix

    International Nuclear Information System (INIS)

    2017-01-01

    Nuclear new build projects are very particular investment proposals, which are unlikely to be undertaken on a straightforward economic basis by equity shareholders and by lenders. This is due to, inter alia, their extended life cycles, their very long term underlying commitments vis-à-vis waste management and decommissioning, the evolving nature of their risk management and the magnitude of their financing requirements. In addition, other factors also apply, all implying a degree of political involvement that makes the investment case even more complicated. As a result of the recent financial and economic crisis, the availability of sizable budgets from public sector players for long term investments in NPPs has been under stress in various parts of the world for a number of years now, and the situation is unlikely to change dramatically in the near future with many State budgets in need of rebalancing, particularly in Europe. The capacity of private sector stakeholders to take over the responsibility for funding such investments has also been challenged following the impact of, inter alia, the liquidity crunch on banks’ funding strategies in Europe during summer 2011, the recent macroeconomic policies on leverage, or the latest regulation that, ultimately, tends to re-direct the banks’ debt lending activities towards transactions requiring financing with shorter maturities. Within this context and among the range of financing instruments that are available and that offer long term maturities, export finance remains a tool of reference for various stakeholders, including the providers (e.g. sellers) of equipment and services and the lending banks. Furthermore, the characteristics of this product make it also perfectly compatible with the requirements of the financing plans typically put in place to fund large, capital intensive investments in infrastructure, such as NPPs.

  4. Nuclear variants of bone morphogenetic proteins

    Directory of Open Access Journals (Sweden)

    Meinhart Christopher A

    2010-03-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts. Results In all three proteins, a bipartite nuclear localization signal (NLS was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5 containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle. Conclusions The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.

  5. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

    Science.gov (United States)

    Jackson, Brian R.; Boyne, James R.; Noerenberg, Marko; Taylor, Adam; Hautbergue, Guillaume M.; Walsh, Matthew J.; Wheat, Rachel; Blackbourn, David J.; Wilson, Stuart A.; Whitehouse, Adrian

    2011-01-01

    The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. PMID:21814512

  6. Soluble components of the flagellar export apparatus, FliI, FliJ, and FliH, do not deliver flagellin, the major filament protein, from the cytosol to the export gate.

    Science.gov (United States)

    Sajó, Ráchel; Liliom, Károly; Muskotál, Adél; Klein, Agnes; Závodszky, Péter; Vonderviszt, Ferenc; Dobó, József

    2014-11-01

    Flagella, the locomotion organelles of bacteria, extend from the cytoplasm to the cell exterior. External flagellar proteins are synthesized in the cytoplasm and exported by the flagellar type III secretion system. Soluble components of the flagellar export apparatus, FliI, FliH, and FliJ, have been implicated to carry late export substrates in complex with their cognate chaperones from the cytoplasm to the export gate. The importance of the soluble components in the delivery of the three minor late substrates FlgK, FlgL (hook-filament junction) and FliD (filament-cap) has been convincingly demonstrated, but their role in the transport of the major filament component flagellin (FliC) is still unclear. We have used continuous ATPase activity measurements and quartz crystal microbalance (QCM) studies to characterize interactions between the soluble export components and flagellin or the FliC:FliS substrate-chaperone complex. As controls, interactions between soluble export component pairs were characterized providing Kd values. FliC or FliC:FliS did not influence the ATPase activity of FliI alone or in complex with FliH and/or FliJ suggesting lack of interaction in solution. Immobilized FliI, FliH, or FliJ did not interact with FliC or FliC:FliS detected by QCM. The lack of interaction in the fluid phase between FliC or FliC:FliS and the soluble export components, in particular with the ATPase FliI, suggests that cells use different mechanisms for the export of late minor substrates, and the major substrate, FliC. It seems that the abundantly produced flagellin does not require the assistance of the soluble export components to efficiently reach the export gate. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Integration of renewable energies and nuclear power into North African Energy Systems: An analysis of energy import and export effects

    International Nuclear Information System (INIS)

    Supersberger, Nikolaus; Fuehrer, Laura

    2011-01-01

    The North African countries Morocco, Algeria, Tunisia, Libya and Egypt have been and are currently experiencing rapid growth in energy demand. This development confronts their political leaders with the question of how to expand or diversify their countries' generation capacities. In this context, renewable energies and nuclear power constitute options that have rarely been exploited so far in the region. This article analyzes the drawbacks and benefits of both alternatives, with a special focus on import and export dynamics. When attempting to make the strategic decision between renewables and atomic power, North African regional specifics and circumstances have to be taken into account. Hence, in a first step, the article characterizes the energy systems of the North African countries and presents scenarios for their future development. In a second step, it scrutinizes the energy challenges these states face in terms of domestic concerns and foreign affairs. Finally, a case study of Algeria is used to demonstrate how renewable energies, but not nuclear power, are able to respond to North African energy challenges. - Research highlights: → Using nuclear power would require fuel imports over the entire operation time. → Hence, energy exporters (Algeria, Libya) would become dependent on fuel imports. → Renewable energies can make North African countries less fuel import dependent. → Nuclear technologies would have to be imported over the whole life cycle of plants. → Domestic production for renewables technologies could be established after a first phase of technology imports.

  8. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization.

    Science.gov (United States)

    Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

    2010-11-01

    We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment.

  9. Export of recombinant proteins in Escherichia coli using ABC transporter with an attached lipase ABC transporter recognition domain (LARD

    Directory of Open Access Journals (Sweden)

    Moon Yuseok

    2009-01-01

    Full Text Available Abstract Background ATP binding cassette (ABC transporter secretes the protein through inner and outer membranes simultaneously in gram negative bacteria. Thermostable lipase (TliA of Pseudomonas fluorescens SIK W1 is secreted through the ABC transporter. TliA has four glycine-rich repeats (GGXGXD in its C-terminus, which appear in many ABC transporter-secreted proteins. From a homology model of TliA derived from the structure of P. aeruginosa alkaline protease (AprA, lipase ABC transporter domains (LARDs were designed for the secretion of fusion proteins. Results The LARDs included four glycine-rich repeats comprising a β-roll structure, and were added to the C-terminus of test proteins. Either Pro-Gly linker or Factor Xa site was added between fusion proteins and LARDs. We attached different length of LARDs such as LARD0, LARD1 or whole TliA (the longest LARD to three types of proteins; green fluorescent protein (GFP, epidermal growth factor (EGF and cytoplasmic transduction peptide (CTP. These fusion proteins were expressed in Escherichia coli together with ABC transporter of either P. fluorescens or Erwinia chrysanthemi. Export of fusion proteins with the whole TliA through the ABC transporter was evident on the basis of lipase enzymatic activity. Upon supplementation of E. coli with ABC transporter, GFP-LARDs and EGF-LARDs were excreted into the culture supernatant. Conclusion The LARDs or whole TliA were attached to C-termini of model proteins and enabled the export of the model proteins such as GFP and EGF in E. coli supplemented with ABC transporter. These results open the possibility for the extracellular production of recombinant proteins in Pseudomonas using LARDs or TliA as a C-terminal signal sequence.

  10. The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

    Science.gov (United States)

    Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

    2017-11-01

    Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

  11. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-07-01

    The document reproduces the text of the notes verbales dated 15 May 1992, received by the Director General from the Resident Representatives to the Agency of Australia, Austria, Belgium, Bulgaria, Canada, Czech and Slovak Federal Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, Russia Federation, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology and the Guidelines for Transfer of Nuclear-Related Dual-Use Equipment, Material and Related Technology. An Annex to these Guidelines contains the list of Nuclear-Related Dual-Use Equipment and Materials and Related Technology

  12. Nuclear transport factor directs localization of protein synthesis during mitosis

    NARCIS (Netherlands)

    Bogaart, Geert van den; Meinema, Anne C.; Krasnikov, Viktor; Veenhoff, Liesbeth M.; Poolman, Bert

    Export of messenger RNA from the transcription site in the nucleus and mRNA targeting to the translation site in the cytoplasm are key regulatory processes in protein synthesis. In yeast, the mRNA-binding proteins Nab2p and Nab4p/Hrp1p accompany transcripts to their translation site, where the

  13. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2006-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology

  14. Communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1992-05-01

    The document reproduces the text of the letters dated 2 March 1992, received by the Director General of the IAEA from the Resident Representatives to the Agency of Australia, Austria, Canada, Czechoslovakia, Denmark, Finland, the Federal Republic of Germany, Greece, Hungary, Ireland, Japan, Luxemburg, the Netherlands, Norway, Poland, Romania, Sweden, the United Kingdom of Great Britain and Northern Ireland and the United States of America regarding the export of nuclear material and of certain categories of equipment and other material, namely plants for the production of heavy water, deuterium and deuterium compound and equipment especially designed or prepared thereof

  15. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2006-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology [es

  16. Communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received a letter dated 7 October 1993 from the Permanent Mission of Bulgaria, letters dated 8 October 1993 from the Permanent Missions of Australia, Austria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, the Netherlands, Norway, Portugal, the Russian Federation, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, the United States of America, and a letter dated 11 October 1993 from the Permanent Mission of Poland to the International Atomic Energy Agency concerning the export of nuclear material and of certain categories of equipment and other material. Text of the letter is presented

  17. Communications received from Member States regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1994-08-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania [es

  18. Communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1990-02-01

    The document reproduces the text of the letters and their annex dated 1 December 1989 received by the Director General of the IAEA from the Resident Representatives to the Agency of the following Member States: Australia, Canada, Czechoslovakia, Finland, the German Democratic Republic, Greece, Hungary, Japan, the Netherlands, Norway, Sweden, the Union of Soviet Socialist Republics, the United Kingdom of Great Britain and Northern Ireland and the United States of America concerning the commitments of these Member States under Article III paragraph 2, of the Treaty on the Non-Proliferation of Nuclear Weapons. It refers to the export of the equipment especially designed or prepared for the separation of isotopes of uranium

  19. Communications received from Member States regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1994-01-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania [fr

  20. Nuclear pore complex protein mediated nuclear localization of dicer protein in human cells.

    Directory of Open Access Journals (Sweden)

    Yoshinari Ando

    Full Text Available Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein.

  1. Quantification of the physiochemical constraints on the export of spider silk proteins by Salmonella type III secretion

    Directory of Open Access Journals (Sweden)

    Voigt Christopher A

    2010-10-01

    Full Text Available Abstract Background The type III secretion system (T3SS is a molecular machine in gram negative bacteria that exports proteins through both membranes to the extracellular environment. It has been previously demonstrated that the T3SS encoded in Salmonella Pathogenicity Island 1 (SPI-1 can be harnessed to export recombinant proteins. Here, we demonstrate the secretion of a variety of unfolded spider silk proteins and use these data to quantify the constraints of this system with respect to the export of recombinant protein. Results To test how the timing and level of protein expression affects secretion, we designed a hybrid promoter that combines an IPTG-inducible system with a natural genetic circuit that controls effector expression in Salmonella (psicA. LacO operators are placed in various locations in the psicA promoter and the optimal induction occurs when a single operator is placed at the +5nt (234-fold and a lower basal level of expression is achieved when a second operator is placed at -63nt to take advantage of DNA looping. Using this tool, we find that the secretion efficiency (protein secreted divided by total expressed is constant as a function of total expressed. We also demonstrate that the secretion flux peaks at 8 hours. We then use whole gene DNA synthesis to construct codon optimized spider silk genes for full-length (3129 amino acids Latrodectus hesperus dragline silk, Bombyx mori cocoon silk, and Nephila clavipes flagelliform silk and PCR is used to create eight truncations of these genes. These proteins are all unfolded polypeptides and they encompass a variety of length, charge, and amino acid compositions. We find those proteins fewer than 550 amino acids reliably secrete and the probability declines significantly after ~700 amino acids. There also is a charge optimum at -2.4, and secretion efficiency declines for very positively or negatively charged proteins. There is no significant correlation with hydrophobicity

  2. Communications Received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material. Two Further Communications dated 26 September 1975

    International Nuclear Information System (INIS)

    1975-01-01

    On 3 October 1975 the Director General received a letter from the Resident Representative of the Netherlands to the Agency transmitting two communications dated 10 September from the Minister for Foreign Affairs of Luxembourg dealing respectively with the export of nuclear material and the export of certain categories of equipment and other material. The Resident Representative requested that all Members be informed of the contents of the two communications, and they are accordingly reproduced below

  3. Pakistan's national legislation entitled: 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'

    International Nuclear Information System (INIS)

    2004-01-01

    The Director General has received a letter from the Permanent Mission of Pakistan, dated 4 November 2004, concerning Pakistan's national legislation entitled 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'. As requested by the Permanent Mission of Pakistan, the letter and the Export Control Act of 2004, are reproduced herein for the information of the Member States

  4. Communication from the Permanent Mission of Cyprus to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2001-01-01

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of Cyprus providing information on the export policies and practices of the Government of Cyprus with respect to the export of nuclear material, equipment and technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment to the Note Verbale was issued previously as INFCIRC/254/Rev. 4/Part 1

  5. Multiple Export Mechanisms for mRNAs

    Science.gov (United States)

    Delaleau, Mildred; Borden, Katherine L. B.

    2015-01-01

    Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

  6. Cooperation of nuclear manpower development between Viet Nam and Korea in order to enhance establishment of infrastructure in exporting nuclear technology to Viet Nam

    International Nuclear Information System (INIS)

    Lee, E. J.; Han, K. W.; Park, J. K.; Kim, Y. T.; Nam, Y. M.; Jang, Y. H.; Yang, M. H.

    2003-08-01

    Through this project, KAERI provided OJT Programme to 3 nuclear experts of Viet Nam at the KAERI for 3 months as a cooperation of human resource development in the field of nuclear policy, nuclear safety analysis and thermo hydraulic. We could have publicity activities of S/W and H/W then achieve an advantage position of economical and technical in exporting nuclear technology to Viet Nam. Also we have provided a training course and seminar for a high-level delegation of nuclear policy decision makers, which is consisted of 5 deputy ministers and general directors of Viet Nam in Korea. Thus we could have Vietnamese who are favoring Korea. The KAERI will also prepare a data base of trained Vietnamese in Korea for the maximum utilization of them in cooperating with Viet Nam. We accomplished the cooperation of human resource development and providing program and curriculum of the nuclear education and training in Viet Nam. Furthermore, it is expected that the enhancement of nuclear technical cooperation between Viet Nam and Korea and the nuclear human resource development

  7. Cooperation of nuclear manpower development between Viet Nam and Korea in order to enhance establishment of infrastructure in exporting nuclear technology to Viet Nam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E. J.; Han, K. W.; Park, J. K.; Kim, Y. T.; Nam, Y. M.; Jang, Y. H.; Yang, M. H

    2003-08-15

    Through this project, KAERI provided OJT Programme to 3 nuclear experts of Viet Nam at the KAERI for 3 months as a cooperation of human resource development in the field of nuclear policy, nuclear safety analysis and thermo hydraulic. We could have publicity activities of S/W and H/W then achieve an advantage position of economical and technical in exporting nuclear technology to Viet Nam. Also we have provided a training course and seminar for a high-level delegation of nuclear policy decision makers, which is consisted of 5 deputy ministers and general directors of Viet Nam in Korea. Thus we could have Vietnamese who are favoring Korea. The KAERI will also prepare a data base of trained Vietnamese in Korea for the maximum utilization of them in cooperating with Viet Nam. We accomplished the cooperation of human resource development and providing program and curriculum of the nuclear education and training in Viet Nam. Furthermore, it is expected that the enhancement of nuclear technical cooperation between Viet Nam and Korea and the nuclear human resource development.

  8. The role of bilateral agreements for cooperation in establishing international norms for nuclear exportation

    International Nuclear Information System (INIS)

    Rowden, M.A.; Kraemer, J.R.

    1986-01-01

    It seems unlikely that a broad multilateral political consensus on the appropriate nuclear control norms will soon be achieved. Bilateral nuclear cooperation agreements will continue to be the dominant political instruments governing international nuclear commerce. Recent developments make the authors optimistic that flexible implementation of the Nuclear Non-Proliferation Act of 1978 will permit a more effective U.S. policy in the field of nuclear commerce. (CW) [de

  9. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2005-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales dated 25 October 2004 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Brazil, Canada, Cyprus, Czech Republic, Estonia, Finland, France, Greece, Hungary, Italy, Japan, Malta, Netherlands, Norway, Republic of Korea, South Africa, Spain, Sweden, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear materials, equipment and technology. The purpose of the Notes Verbales is to provide further information on those Governments' guidelines for nuclear transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to these Notes Verbales is also reproduced in full

  10. Communications received from certain Member States regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-05-16

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 28 February 2003, from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Canada, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Kazakhstan, Latvia, Netherlands, Norway, Poland, Portugal, the Republic of Korea, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America, relating to the export of nuclear material, equipment and technology. The purpose of the Note Verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to the Notes Verbales is also reproduced in full.

  11. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-16

    The document contains the text of note verbales dated 17 October 1996 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. A similar note verbal dated 30 July 1997 has been received by the Director General of the IAEA from the Resident Representative to the Agency of Brazil. The purpose of the notes verbale is to provide further information on those Governments` Guidelines for Nuclear Transfers.

  12. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-02-23

    The Director General of the International Atomic Energy Agency has received Notes Verbales dated 25 October 2004 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Brazil, Canada, Cyprus, Czech Republic, Estonia, Finland, France, Greece, Hungary, Italy, Japan, Malta, Netherlands, Norway, Republic of Korea, South Africa, Spain, Sweden, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear materials, equipment and technology. The purpose of the Notes Verbales is to provide further information on those Governments' guidelines for nuclear transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to these Notes Verbales is also reproduced in full.

  13. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-24

    The document contains the text of note verbales dated 30 September 1997 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information about the Guidelines for Transfers of Nuclear-related Dual-use Equipment, material and related Technology in accordance with which the relevant Governments act.

  14. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1997-01-01

    The document contains the text of note verbales dated 17 October 1996 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. A similar note verbal dated 30 July 1997 has been received by the Director General of the IAEA from the Resident Representative to the Agency of Brazil. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers

  15. Communications received from certain Member States regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2003-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 28 February 2003, from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Canada, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Kazakhstan, Latvia, Netherlands, Norway, Poland, Portugal, the Republic of Korea, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America, relating to the export of nuclear material, equipment and technology. The purpose of the Note Verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to the Notes Verbales is also reproduced in full

  16. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbale, dated 31 August 2001, from the Resident Representatives to the Agency of Argentina, Austria, Belarus, Belgium, Brazil, Bulgaria, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Luxembourg, Netherlands, New Zealand, Portugal, Republic of Korea, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United States and the United Kingdom, relating to the export of nuclear material, equipment and technology. The purpose of the Notes Verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbale is attached. The attachment to the Notes Verbale is also reproduced in full

  17. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1998-01-01

    The document contains the text of note verbales dated 30 September 1997 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information about the Guidelines for Transfers of Nuclear-related Dual-use Equipment, material and related Technology in accordance with which the relevant Governments act

  18. Nuclear Trafficking of the Rabies Virus Interferon Antagonist P-Protein Is Regulated by an Importin-Binding Nuclear Localization Sequence in the C-Terminal Domain.

    Directory of Open Access Journals (Sweden)

    Caitlin L Rowe

    Full Text Available Rabies virus P-protein is expressed as five isoforms (P1-P5 which undergo nucleocytoplasmic trafficking important to roles in immune evasion. Although nuclear import of P3 is known to be mediated by an importin (IMP-recognised nuclear localization sequence in the N-terminal region (N-NLS, the mechanisms underlying nuclear import of other P isoforms in which the N-NLS is inactive or has been deleted have remained unresolved. Based on the previous observation that mutation of basic residues K214/R260 of the P-protein C-terminal domain (P-CTD can result in nuclear exclusion of P3, we used live cell imaging, protein interaction analysis and in vitro nuclear transport assays to examine in detail the nuclear trafficking properties of this domain. We find that the effect of mutation of K214/R260 on P3 is largely dependent on nuclear export, suggesting that nuclear exclusion of mutated P3 involves the P-CTD-localized nuclear export sequence (C-NES. However, assays using cells in which nuclear export is pharmacologically inhibited indicate that these mutations significantly inhibit P3 nuclear accumulation and, importantly, prevent nuclear accumulation of P1, suggestive of effects on NLS-mediated import activity in these isoforms. Consistent with this, molecular binding and transport assays indicate that the P-CTD mediates IMPα2/IMPβ1-dependent nuclear import by conferring direct binding to the IMPα2/IMPβ1 heterodimer, as well as to a truncated form of IMPα2 lacking the IMPβ-binding autoinhibitory domain (ΔIBB-IMPα2, and IMPβ1 alone. These properties are all dependent on K214 and R260. This provides the first evidence that P-CTD contains a genuine IMP-binding NLS, and establishes the mechanism by which P-protein isoforms other than P3 can be imported to the nucleus. These data underpin a refined model for P-protein trafficking that involves the concerted action of multiple NESs and IMP-binding NLSs, and highlight the intricate regulation of P-protein

  19. Nuclear import and export signals of human cohesins SA1/STAG1 and SA2/STAG2 expressed in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Leszek J Tarnowski

    Full Text Available BACKGROUND: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in transcriptional regulation as well. The molecular basis of this functional divergence is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In silico analysis indicates numerous putative nuclear localization (NLS and export (NES signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the N-terminal NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in yeast and is localized to the C-terminus. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The reported difference in the organization between the two SA homologues may also be relevant to their partially divergent functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and human cells.

  20. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka, E-mail: kinjo@sci.hokudai.ac.jp

    2015-07-31

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS{sup SV40}) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS{sup SV40} in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS{sup SV40} formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS{sup SV40} likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS{sup SV40} can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. - Highlights: • Nuclear localization signal-tagged GFP (GFP-NLS) showed clear nuclear localization. • The GFP-NLS dynamically localized not only in the nucleoplasm, but also to the nucleolus. • The nuclear localization of GFP-NLS results from transient oligomerization mediated via RNA binding. • Our NLS-tagging procedure is ideal for use in artificial sequestration of proteins in the nucleus.

  1. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

    International Nuclear Information System (INIS)

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka

    2015-01-01

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS SV40 ) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS SV40 in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS SV40 formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS SV40 likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS SV40 can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. - Highlights: • Nuclear localization signal-tagged GFP (GFP-NLS) showed clear nuclear localization. • The GFP-NLS dynamically localized not only in the nucleoplasm, but also to the nucleolus. • The nuclear localization of GFP-NLS results from transient oligomerization mediated via RNA binding. • Our NLS-tagging procedure is ideal for use in artificial sequestration of proteins in the nucleus

  2. Identification of multidrug resistance protein 1 (MRP1/ABCC1) as a molecular gate for cellular export of cobalamin

    DEFF Research Database (Denmark)

    Beedholm-Ebsen, Rasmus; van de Wetering, Koen; Hardlei, Tore

    2010-01-01

    transporters by cellular gene silencing showed a role in cellular Cbl efflux of the ATP-binding cassette (ABC)-drug transporter, ABCC1, alias multidrug resistance protein 1 (MRP1), which is present in the basolateral membrane of intestinal epithelium and in other cells. The ability of MRP1 to mediate ATP...... and kidney. In contrast, Cbl accumulates in the terminal part of the intestine of these mice, suggesting a functional malabsorption because of a lower epithelial basolateral Cbl efflux. The identification of this Cbl export mechanism now allows the delineation of a coherent pathway for Cbl trafficking from...

  3. A study on strengthening measures of non-proliferation regime through the export control system of sensitive materials, equipment and technology related to nuclear activities

    International Nuclear Information System (INIS)

    Kikuchi, Masahiro; Kurosawa, Mitsuru; Komizo, Yasuyoshi

    2004-01-01

    The strengthened safeguards caused from safeguards experiences to Iraq and DPRK leads to the expansion of the IAEA's activities for verification of all nuclear activities as well as verification of nuclear material in the States. The purpose of the activities, of course, includes detection of undeclared exports and imports of specified equipment and non-nuclear material. The Additional Protocol to the agreements between States and the IAEA for the application of safeguards requires to the States to declare the exports and imports information regarding specified equipment and non-nuclear material corresponding to the export control list that is established by the nuclear suppliers group. The Additional Protocol also insists the IAEA's right to access to the location identified by the State to resolve a question related to the declarations. Recently, the IAEA detected the black market group of the sensitive materials, equipment and technologies relevant to the nuclear proliferation through the safeguards activities to Iran and Libya. International community stated deeply concerns to the indecent facts. This paper would discuss and propose the supplemental strengthening measures of non-proliferation regime by effective combination of the safeguards activities under additional protocol and the export control regime. (author)

  4. Design and construction of nuclear power plants for export. Adaptation of a reference plant from a series in a national power generating program

    International Nuclear Information System (INIS)

    Marcaillou, J.; Haond, H.

    1977-01-01

    The recent evolution of primary energy supplies places those countries having a nuclear industry in an exporting role. Exporting countries have generally developed a limited number of national reactor types and attempt to extend their manufacture with as few changes as possible. The E.D.F. in France is implementing an important PWR 900 MW program based on FRAMATOME nuclear reactors, initially conceived by WESTINGHOUSE. Such standardization poses certain problems for the importing countries. These problems and ways in which they can be solved are discussed [fr

  5. Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins.

    Science.gov (United States)

    Li, Sanshu; Smith, Kathryn D; Davis, Jared H; Gordon, Patricia B; Breaker, Ronald R; Strobel, Scott A

    2013-11-19

    Fluorine is an abundant element and is toxic to organisms from bacteria to humans, but the mechanisms by which eukaryotes resist fluoride toxicity are unknown. The Escherichia coli gene crcB was recently shown to be regulated by a fluoride-responsive riboswitch, implicating it in fluoride response. There are >8,000 crcB homologs across all domains of life, indicating that it has an important role in biology. Here we demonstrate that eukaryotic homologs [renamed FEX (fluoride exporter)] function in fluoride export. FEX KOs in three eukaryotic model organisms, Neurospora crassa, Saccharomyces cerevisiae, and Candida albicans, are highly sensitized to fluoride (>200-fold) but not to other halides. Some of these KO strains are unable to grow in fluoride concentrations found in tap water. Using the radioactive isotope of fluoride, (18)F, we developed an assay to measure the intracellular fluoride concentration and show that the FEX deletion strains accumulate fluoride in excess of the external concentration, providing direct evidence of FEX function in fluoride efflux. In addition, they are more sensitive to lower pH in the presence of fluoride. These results demonstrate that eukaryotic FEX genes encode a previously unrecognized class of fluoride exporter necessary for survival in standard environmental conditions.

  6. Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells.

    Science.gov (United States)

    Hodroj, Dana; Serhal, Kamar; Maiorano, Domenico

    2017-09-03

    The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation. In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore. Here we review recent findings related to an additional Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated during collision between transcription and replication, and upon DNA damage. Activation of a DNA damage response pathway dependent upon the ATR kinase, a major regulator of replication fork progression, stimulates translocation of the Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA double strand breaks only in proliferating cells. Overall these observations put forward Ddx19 as an important novel mediator of the crosstalk between transcription and replication.

  7. Communications received from Member States regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania. In the light of the wish expressed at the end of each letter, the text of the letters is attached hereto

  8. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear-related dual-use transfers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex.

  9. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear-related dual-use transfers

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex

  10. 75 FR 44072 - Export and Import of Nuclear Equipment and Material; Updates and Clarifications

    Science.gov (United States)

    2010-07-28

    ... does not feel that placing an additional regulatory compliance burden on the public is warranted at this time. The NRC believes that any questions the public may have regarding compliance with exclusion... globalization of the nuclear industry, U.S. nuclear companies are outsourcing more and more items, including...

  11. Project for export system construction of nuclear equipment to IAEA; survey on current market status of the nuclear related international organizations and the domestic possible suppliers

    Energy Technology Data Exchange (ETDEWEB)

    Min, T S; Cho, H K; Kim, H J [Korea Atomic Industrial Forum, Seoul (Korea)

    2001-05-01

    Republic of Korea are keeping the dynamic activities in IAEA as the 8th advanced nuclear country over the world but has occupied very low late less than 0.01% in supplying the equipments to IAEA. About 6,000 nuclear equipment suppliers are registered in IAEA Supply Roster over the world but only 3 Suppliers of our country are registered in IAEA Supply Roster. The supply of nuclear industrial products equivalent to about 100 million dollars into IAEA market will endorse not only the international authorization for our technology and products but also give contribution to activate the domestic nuclear industries in order to increase its expert. The explanation for IAEA procurement market to the 53 nuclear companies will be made on May 16, 2001, and the participants for the export of their goods will be selected. And then we will do all possible supports by the government and related organizations for them to register in IAEA Supply Roster. 21 refs. (Author)

  12. Creation of nuclear power stations for export. Adapting a reference power station from the technical level of a national programme

    International Nuclear Information System (INIS)

    Marcaillou, J.; Haond, H.; Py, J.P.

    1977-01-01

    The recent evolution of primary energy supplies places those countries with a nuclear industry in an exporting role. Exporting countries have generally developed a limited number of national reactor types and attempt to extend their manufacture with as few changes as possible. The EDF in France is implementing an important 900-MW(e) PWR programme based on Framatome nuclear reactors, initially conceived by Westinghouse. Standardization imposes constraints, has limits, but offers incontestable advantages in terms of reliability, availability and security. These advantages were highly appreciated during the introduction into service of conventional thermal loads. Importing countries are all concerned to purchase a proven model. However, various local restrictions are often present, which are usually different from those accounted for in the export model, thus resulting in a need for modification. The different ways of considering the inescapable constraints can be analysed and their influence on the 'disfigurement' of the reactor model can be examined. Some of these constraints are connected with characteristics of the site. The nature of the soil and the seismicity influence the foundation and the depth of the installation and the choice between a foundation on antiseismic supports or structural reinforcement. The hydrology (risk of flooding or of deviation of the cold source) influences the choice between elevation of the installation and a protective dike, and also the stand-by coolant circuit. The atmospheric conditions and the temperature of cooling water influence the materials and their conditioning as well as the power level of the station. The surrounding demography influences the waste treatment systems. The characteristics of the electricity network influence the plan of the electric power supply and the conditions of operation. Finally, the characteristics of the personnel of the undertaking provide training problems. Other parameters to be taken into

  13. In the matter of the application of the Westinghouse Electric Corporation for the export of pressurized water reactor to Asociacion Nuclear ASCO II, Barcelona, Spain

    International Nuclear Information System (INIS)

    Rowden, M.A.; Mason, E.A.; Gilinsky, V.; Kennedy, R.T.

    1976-01-01

    The paper contains the text of a decision of the US NRC that the export of the ASCO nuclear power unit II to Spain would not be inimical to the common defense and security of the United States, so that there are no objections to issue the license to Westinghouse Electric Corporation. Furthermore the paper contains the dissenting opinion of Commissioner Gilinsky. (HP) [de

  14. Communication from the Permanent Mission of France to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of France to the IAEA providing information on the policies and practices of the Government of France with respect to the export of nuclear material, equipment and technology

  15. Communication of 12 June 2000 received from the Ministry of Foreign Affairs of the Republic of Slovenia regarding Slovenia's nuclear export policies and practices

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale dated 12 June 2000 received by the Secretariat of the IAEA from the Ministry of Foreign Affairs of the Republic of Slovenia providing information on the nuclear export policies and practices of the Government of the Republic of Slovenia

  16. Serotype-specific Differences in Dengue Virus Non-structural Protein 5 Nuclear Localization*

    Science.gov (United States)

    Hannemann, Holger; Sung, Po-Yu; Chiu, Han-Chen; Yousuf, Amjad; Bird, Jim; Lim, Siew Pheng; Davidson, Andrew D.

    2013-01-01

    The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes. PMID:23770669

  17. Serotype-specific differences in dengue virus non-structural protein 5 nuclear localization.

    Science.gov (United States)

    Hannemann, Holger; Sung, Po-Yu; Chiu, Han-Chen; Yousuf, Amjad; Bird, Jim; Lim, Siew Pheng; Davidson, Andrew D

    2013-08-02

    The four serotypes of dengue virus (DENV-1 to -4) cause the most important arthropod-borne viral disease of humans. DENV non-structural protein 5 (NS5) contains enzymatic activities required for capping and replication of the viral RNA genome that occurs in the host cytoplasm. However, previous studies have shown that DENV-2 NS5 accumulates in the nucleus during infection. In this study, we examined the nuclear localization of NS5 for all four DENV serotypes. We demonstrate for the first time that there are serotypic differences in NS5 nuclear localization. Whereas the DENV-2 and -3 proteins accumulate in the nucleus, DENV-1 and -4 NS5 are predominantly if not exclusively localized to the cytoplasm. Comparative studies on the DENV-2 and -4 NS5 proteins revealed that the difference in DENV-4 NS5 nuclear localization was not due to rapid nuclear export but rather the lack of a functional nuclear localization sequence. Interaction studies using DENV-2 and -4 NS5 and human importin-α isoforms failed to identify an interaction that supported the differential nuclear localization of NS5. siRNA knockdown of the human importin-α isoform KPNA2, corresponding to the murine importin-α isoform previously shown to bind to DENV-2 NS5, did not substantially affect DENV-2 NS5 nuclear localization, whereas knockdown of importin-β did. The serotypic differences in NS5 nuclear localization did not correlate with differences in IL-8 gene expression. The results show that NS5 nuclear localization is not strictly required for virus replication but is more likely to have an auxiliary function in the life cycle of specific DENV serotypes.

  18. Canada's reactor exports

    International Nuclear Information System (INIS)

    Morrison, R.W.

    1981-01-01

    A brief sketch of the development of Canada's nuclear exports is presented and some of the factors which influence the ability to export reactors have been identified. The potential market for CANDUs is small and will develop slowly. The competition will be tough. There are few good prospects for immediate export orders in the next two or three years. Nonetheless there are reasonable opportunities for CANDU exports, especially in the mid-to-late 1980s. Such sales could be of great benefit to Canada and could do much to sustain the domestic nuclear industry. Apart from its excellent economic and technical performance, the main attraction of the CANDU seems to be the autonomy it confers on purchasing countries, the effectiveness with which the associated technology can be transferred, and the diversification it offers to countries which wish to reduce their dependence on the major industrial suppliers. Each sales opportunity is unique, and marketing strategy will have to be tailored to the customer's needs. Over the next decade, the factors susceptible to Canadian government action which are most likely to influence CANDU exports will be the political commitment of the government to those reactor exports, the performance established by the four 600 MWe CANDUs now nearing completion, the continuing successful operation of the nuclear program in Ontario, and the co-ordination of the different components of Canada's nuclear program (AECL, nuclear industry, utilities, and government) in putting forth a coherent marketing effort and following through with effective project management

  19. Function of Nup98 subtypes and their fusion proteins, Nup98-TopIIβ and Nup98-SETBP1 in nuclear-cytoplasmic transport.

    Science.gov (United States)

    Saito, Shoko; Yokokawa, Takafumi; Iizuka, Gemmei; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2017-05-20

    Nup98 is a component of the nuclear pore complex. The nup98-fusion genes derived by chromosome translocations are involved in hematopoietic malignancies. Here, we investigated the functions of Nup98 isoforms and two unexamined Nup98-fusion proteins, Nup98-TopIIβ and Nup98-SETBP1. We first demonstrated that two Nup98 isoforms are expressed in various mouse tissues and similarly localized in the nucleus and the nuclear envelope. We also showed that Nup98-TopIIβ and Nup98-SETBP1 are localized in the nucleus and partially co-localized with full-length Nup98 and a nuclear export receptor XPO1. We demonstrated that Nup98-TopIIβ and Nup98-SETBP1 negatively regulate the XPO1-mediated protein export. Our results will contribute to the understanding of the molecular mechanism by which the Nup98-fusion proteins induce tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Communication from the Permanent Mission of Australia to the International Atomic Energy Agency regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of Australia, dated 31 August 2001, providing information on the export policies and practices of the Government of Australia with respect to the export of nuclear material, equipment and technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment referenced in the Note Verbale was issued previously as INFCIRC/254/Rev. 5/Part 1

  1. US exports

    International Nuclear Information System (INIS)

    Schrage, W.E.

    1991-01-01

    This paper reports on the past, present, and future of US coal exports. It is expected that in the 1990's, the following factors will be evident: Significant increases in coal production and port capacity in Australia and South Africa, but little in Canada; Potentially significant increase in coal production and port capacity in Colombia, Venezuela and Indonesia; Continued movement away from subsidized indigenous coal production in Europe and Japan. A substantial growth in world coal trade; Stronger growth in energy demand in the 1990s than in the 1980s; Significantly fewer additions to nuclear generating capacity in the 1990s than in the 1980s; Reduced coal production in Eastern Europe from that of the 1980s; Greater caution will be exercised in putting in new coal production capacity

  2. 10 CFR 110.8 - List of nuclear facilities and equipment under NRC export licensing authority.

    Science.gov (United States)

    2010-01-01

    ... isotopes of uranium (source material or special nuclear material) including gas centrifuge plants, gaseous diffusion plants, aerodynamic enrichment plants, chemical exchange or ion exchange enrichment plants, laser... of uranium. (See appendices to this part for lists of: gas centrifuge equipment—Appendix B; gaseous...

  3. The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1

    Energy Technology Data Exchange (ETDEWEB)

    Shakya, Bikash; Penn, Wesley D.; Nakayasu, Ernesto S.; Lacount, Douglas J.

    2017-09-01

    Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs. Yeast two-hybrid screens with ANK1 and 4.1R identified eight interactions with P. falciparum exported proteins, including an interaction between 4.1R and PF3D7_0402000 (PFD0090c). This interaction was first identified in a large-scale screen (Vignali et al., Malaria J, 7:211, 2008), which also reported an interaction between PF3D7_0402000 and ANK1. We confirmed the interactions of PF3D7_0402000 with 4.1R and ANK1 in pair-wise yeast two-hybrid and co-precipitation assays. In both cases, an intact PHIST domain in PF3D7_0402000 was required for binding. Complex purification followed by mass spectrometry analysis provided additional support for the interaction of PF3D7_0402000 with ANK1 and 4.1R. RBC ghost cells loaded with maltose-binding protein (MBP)-PF3D7_0402000 passed through a metal microsphere column less efficiently than mock- or MBP-loaded controls, consistent with an effect of PF3D7_0402000 on RBC rigidity or membrane stability. This study confirmed the interaction of PF3D7_0402000 with 4.1R in multiple independent assays, provided the first evidence that PF3D7_0402000 also binds to ANK1, and suggested that PF3D7_0402000 affects deformability or membrane stability of uninfected RBC ghosts.

  4. Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

    DEFF Research Database (Denmark)

    Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

    2013-01-01

    . However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...... Mature Epitope Density (MED). Our method, though simple, is capable of identifying promising vaccine targets. Our online software implementation provides a computationally light and reliable analysis of bacterial exoproteins and their potential for vaccines or diagnosis projects against pathogenic...... proteins were confirmed as related. There was no experimental evidence of antigenic or pathogenic contributions for three of the highest MED-scored Mtb proteins. Hence, these three proteins could represent novel putative vaccine and drug targets for Mtb. A web version of MED is publicly available online...

  5. Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE KPT-335 in spontaneous canine cancer: results of a phase I study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1 against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability.Canine tumor cell lines derived from non-Hodgkin lymphoma (NHL, mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed, mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday although biologic activity was observed at 1 mg/kg. Clinical benefit (CB including partial response to therapy (PR, n = 2 and stable disease (SD, n = 7 was observed in 9/14 dogs with NHL with a median time to progression (TTP for responders of 66 days (range 35-256 days. A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days. Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities.This study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer.

  6. The implications of uranium export

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    It is argued that Australia should not enter the business of uranium mining enrichment and export because of the hazards of nuclear power and because there are practical alternatives to the development of nuclear power. (R.L.)

  7. Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding.

    Directory of Open Access Journals (Sweden)

    Yao E Wang

    2010-11-01

    Full Text Available Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4 pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS and the leucine-rich nuclear export signal (NES found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50 of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf" therapeutic against acute NiV infection.

  8. Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins

    OpenAIRE

    Li, Sanshu; Smith, Kathryn D.; Davis, Jared H.; Gordon, Patricia B.; Breaker, Ronald R.; Strobel, Scott A.

    2013-01-01

    Although fluoride is plentiful in the environment and is commonly used at high concentrations in oral hygiene products, little has been known about how biological systems overcome the toxic effects of this anion. We demonstrate that a protein called FEX in many fungi is essential for cell survival in the presence of high fluoride concentrations. The protein is required for the rapid expulsion of cytoplasmic fluoride, indicating that many eukaryotic species that carry FEX genes likely avoid fl...

  9. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    Science.gov (United States)

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  10. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

    2008-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  11. The B7-1 cytoplasmic tail enhances intracellular transport and mammalian cell surface display of chimeric proteins in the absence of a linear ER export motif.

    Directory of Open Access Journals (Sweden)

    Yi-Chieh Lin

    Full Text Available Membrane-tethered proteins (mammalian surface display are increasingly being used for novel therapeutic and biotechnology applications. Maximizing surface expression of chimeric proteins on mammalian cells is important for these applications. We show that the cytoplasmic domain from the B7-1 antigen, a commonly used element for mammalian surface display, can enhance the intracellular transport and surface display of chimeric proteins in a Sar1 and Rab1 dependent fashion. However, mutational, alanine scanning and deletion analysis demonstrate the absence of linear ER export motifs in the B7 cytoplasmic domain. Rather, efficient intracellular transport correlated with the presence of predicted secondary structure in the cytoplasmic tail. Examination of the cytoplasmic domains of 984 human and 782 mouse type I transmembrane proteins revealed that many previously identified ER export motifs are rarely found in the cytoplasmic tail of type I transmembrane proteins. Our results suggest that efficient intracellular transport of B7 chimeric proteins is associated with the structure rather than to the presence of a linear ER export motif in the cytoplasmic tail, and indicate that short (less than ~ 10-20 amino acids and unstructured cytoplasmic tails should be avoided to express high levels of chimeric proteins on mammalian cells.

  12. The human nuclear poly(a-binding protein promotes RNA hyperadenylation and decay.

    Directory of Open Access Journals (Sweden)

    Stefan M Bresson

    Full Text Available Control of nuclear RNA stability is essential for proper gene expression, but the mechanisms governing RNA degradation in mammalian nuclei are poorly defined. In this study, we uncover a mammalian RNA decay pathway that depends on the nuclear poly(A-binding protein (PABPN1, the poly(A polymerases (PAPs, PAPα and PAPγ, and the exosome subunits RRP6 and DIS3. Using a targeted knockdown approach and nuclear RNA reporters, we show that PABPN1 and PAPα, redundantly with PAPγ, generate hyperadenylated decay substrates that are recognized by the exosome and degraded. Poly(A tail extension appears to be necessary for decay, as cordycepin treatment or point mutations in the PAP-stimulating domain of PABPN1 leads to the accumulation of stable transcripts with shorter poly(A tails than controls. Mechanistically, these data suggest that PABPN1-dependent promotion of PAP activity can stimulate nuclear RNA decay. Importantly, efficiently exported RNAs are unaffected by this decay pathway, supporting an mRNA quality control function for this pathway. Finally, analyses of both bulk poly(A tails and specific endogenous transcripts reveals that a subset of nuclear RNAs are hyperadenylated in a PABPN1-dependent fashion, and this hyperadenylation can be either uncoupled or coupled with decay. Our results highlight a complex relationship between PABPN1, PAPα/γ, and nuclear RNA decay, and we suggest that these activities may play broader roles in the regulation of human gene expression.

  13. The Escherichia coli small protein MntS and exporter MntP optimize the intracellular concentration of manganese.

    Directory of Open Access Journals (Sweden)

    Julia E Martin

    2015-03-01

    Full Text Available Escherichia coli does not routinely import manganese, but it will do so when iron is unavailable, so that manganese can substitute for iron as an enzyme cofactor. When intracellular manganese levels are low, the cell induces the MntH manganese importer plus MntS, a small protein of unknown function; when manganese levels are high, the cell induces the MntP manganese exporter and reduces expression of MntH and MntS. The role of MntS has not been clear. Previous work showed that forced MntS synthesis under manganese-rich conditions caused bacteriostasis. Here we find that when manganese is scarce, MntS helps manganese to activate a variety of enzymes. Its overproduction under manganese-rich conditions caused manganese to accumulate to very high levels inside the cell; simultaneously, iron levels dropped precipitously, apparently because manganese-bound Fur blocked the production of iron importers. Under these conditions, heme synthesis stopped, ultimately depleting cytochrome oxidase activity and causing the failure of aerobic metabolism. Protoporphyrin IX accumulated, indicating that the combination of excess manganese and iron deficiency had stalled ferrochelatase. The same chain of events occurred when mutants lacking MntP, the manganese exporter, were exposed to manganese. Genetic analysis suggested the possibility that MntS exerts this effect by inhibiting MntP. We discuss a model wherein during transitions between low- and high-manganese environments E. coli uses MntP to compensate for MntH overactivity, and MntS to compensate for MntP overactivity.

  14. Exploring the Leishmania Hydrophilic Acylated Surface Protein B (HASPB) Export Pathway by Live Cell Imaging Methods.

    Science.gov (United States)

    MacLean, Lorna; Price, Helen; O'Toole, Peter

    2016-01-01

    Leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. The L. major hydrophilic acylated surface protein B (HASPB) is only expressed in infective parasite stages suggesting a role in parasite virulence. HASPB is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical ER-Golgi pathway. Instead HASPB trafficking to and exposure on the parasite plasma membrane requires dual N-terminal acylation. Here, we use live cell imaging methods to further explore this pathway allowing visualization of key events in real time at the individual cell level. These methods include live cell imaging using fluorescent reporters to determine the subcellular localization of wild type and acylation site mutation HASPB18-GFP fusion proteins, fluorescence recovery after photobleaching (FRAP) to analyze the dynamics of HASPB in live cells, and live antibody staining to detect surface exposure of HASPB by confocal microscopy.

  15. A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

    Science.gov (United States)

    Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

    2012-01-01

    Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

  16. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    International Nuclear Information System (INIS)

    Han, Mingyuan; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan

    2017-01-01

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of 126 -LQxxLxxxGL- 135 . In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine arteritis virus.

  17. Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

    Energy Technology Data Exchange (ETDEWEB)

    Han, Mingyuan, E-mail: hanming@umich.edu; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan, E-mail: dyoo@illinois.edu

    2017-05-15

    Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of {sub 126}-LQxxLxxxGL-{sub 135}. In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. - Highlights: •PRRS virus blocks host mRNA nuclear export to the cytoplasm. •PRRSV nsp1β is the viral protein responsible for host mRNA nuclear retention. •SAP domain in nsp1β is essential for host mRNA nuclear retention and type I interferon suppression. •Mutation in the SAP domain of nsp1β causes the loss of function. •Host mRNA nuclear retention by nsp1β is common in the family Arteriviridae, except equine

  18. Integrating complex functions: coordination of nuclear pore complex assembly and membrane expansion of the nuclear envelope requires a family of integral membrane proteins.

    Science.gov (United States)

    Schneiter, Roger; Cole, Charles N

    2010-01-01

    The nuclear envelope harbors numerous large proteinaceous channels, the nuclear pore complexes (NPCs), through which macromolecular exchange between the cytosol and the nucleoplasm occurs. This double-membrane nuclear envelope is continuous with the endoplasmic reticulum and thus functionally connected to such diverse processes as vesicular transport, protein maturation and lipid synthesis. Recent results obtained from studies in Saccharomyces cerevisiae indicate that assembly of the nuclear pore complex is functionally dependent upon maintenance of lipid homeostasis of the ER membrane. Previous work from one of our laboratories has revealed that an integral membrane protein Apq12 is important for the assembly of functional nuclear pores. Cells lacking APQ12 are viable but cannot grow at low temperatures, have aberrant NPCs and a defect in mRNA export. Remarkably, these defects in NPC assembly can be overcome by supplementing cells with a membrane fluidizing agent, benzyl alcohol, suggesting that Apq12 impacts the flexibility of the nuclear membrane, possibly by adjusting its lipid composition when cells are shifted to a reduced temperature. Our new study now expands these findings and reveals that an essential membrane protein, Brr6, shares at least partially overlapping functions with Apq12 and is also required for assembly of functional NPCs. A third nuclear envelope membrane protein, Brl1, is related to Brr6, and is also required for NPC assembly. Because maintenance of membrane homeostasis is essential for cellular survival, the fact that these three proteins are conserved in fungi that undergo closed mitoses, but are not found in metazoans or plants, may indicate that their functions are performed by proteins unrelated at the primary sequence level to Brr6, Brl1 and Apq12 in cells that disassemble their nuclear envelopes during mitosis.

  19. A novel family of plant nuclear envelope-associated proteins.

    Science.gov (United States)

    Pawar, Vidya; Poulet, Axel; Détourné, Gwénaëlle; Tatout, Christophe; Vanrobays, Emmanuel; Evans, David E; Graumann, Katja

    2016-10-01

    This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

    International Nuclear Information System (INIS)

    Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Huebner, Stefan

    2009-01-01

    Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.

  1. A set of enhanced green fluorescent protein concatemers for quantitative determination of nuclear localization signal strength.

    Science.gov (United States)

    Böhm, Jennifer; Thavaraja, Ramya; Giehler, Susanne; Nalaskowski, Marcus M

    2017-09-15

    Regulated transport of proteins between nucleus and cytoplasm is an important process in the eukaryotic cell. In most cases, active nucleo-cytoplasmic protein transport is mediated by nuclear localization signal (NLS) and/or nuclear export signal (NES) motifs. In this study, we developed a set of vectors expressing enhanced GFP (EGFP) concatemers ranging from 2 to 12 subunits (2xEGFP to 12xEGFP) for analysis of NLS strength. As shown by in gel GFP fluorescence analysis and αGFP Western blotting, EGFP concatemers are expressed as fluorescent full-length proteins in eukaryotic cells. As expected, nuclear localization of concatemeric EGFPs decreases with increasing molecular weight. By oligonucleotide ligation this set of EGFP concatemers can be easily fused to NLS motifs. After determination of intracellular localization of EGFP concatemers alone and fused to different NLS motifs we calculated the size of a hypothetic EGFP concatemer showing a defined distribution of EGFP fluorescence between nucleus and cytoplasm (n/c ratio = 2). Clear differences of the size of the hypothetic EGFP concatemer depending on the fused NLS motif were observed. Therefore, we propose to use the size of this hypothetic concatemer as quantitative indicator for comparing strength of different NLS motifs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Communications of 15 November 1999 Received from Member States Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2009-01-01

    The Director General of the International Atomic Energy Agency has received letters of 17 October 1996 from the Resident Representatives of Argentina, Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material [es

  3. Communications of 15 November 1999 Received from Member States Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2000-03-01

    The Director General of the International Atomic Energy Agency has received letters of 17 October 1996 from the Resident Representatives of Argentina, Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material [fr

  4. Communications of 15 November 1999 Received from Member States Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2009-01-01

    The Director General of the International Atomic Energy Agency has received letters of 17 October 1996 from the Resident Representatives of Argentina, Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material

  5. Communications of 30 June 1995 received from Member States regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received letters of 30 June 1995 from the Resident Representative of Argentina, Australia, Austria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary Ireland, Italy, Japan, Luxembourg, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material

  6. Communications of 15 November 1999 Received from Member States Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2000-01-01

    The Director General of the International Atomic Energy Agency has received letters of 17 October 1996 from the Resident Representatives of Argentina, Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material

  7. Communication received from the permanent mission of Austria regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General received a note verbale of 13 June 1996 from Permanent Mission of Austria regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material. In the light of the request expressed at the end of the note verbale, the text of the note verbale is being circulated

  8. Communication received from the Permanent Mission of Sweden regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The document reproduces the text of a note verbale dated 28 June 1996 received by the Director General of IAEA from the Permanent Mission of Sweden through which the Government of Sweden provides, on a voluntary basis, certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material, in order to assist the Agency in the discharge of its safeguards responsibilities

  9. Communication received from the permanent mission of Finland regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General received a note verbale of 8 February 1996 from Permanent Mission of Finland regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material. In the light of the request expressed at the and of the note verbale, the text of the note verbale is being circulated

  10. Integration of mRNP formation and export.

    Science.gov (United States)

    Björk, Petra; Wieslander, Lars

    2017-08-01

    Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA-protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within the interchromatin compartment, making up pools of mRNPs. Here, splicing and polyadenylation can be completed and the mRNPs recruit the major export receptor NXF1. Export competent mRNPs interact with the nuclear pore complex, leading to export, concomitant with compositional and conformational changes of the mRNPs. We summarize the integrated nuclear processes involved in the formation and export of mRNPs.

  11. Communications of 30 November 1995 received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-19

    The Director General has received notes verbales of 30 November 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, The Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for transfers of nuclear-related dual-use equipment, material and related technology.

  12. Communications of 30 November 1995 received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General has received notes verbales of 30 November 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, The Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for transfers of nuclear-related dual-use equipment, material and related technology

  13. Export spillovers

    DEFF Research Database (Denmark)

    Choquette, Eliane; Meinen, Philipp

    2015-01-01

    This paper studies the importance of export spillovers in a firm's decision to enter specific export markets and extends the current state of the literature by assessing different mechanisms through which they may occur, namely (i) labour movement, (ii) intra-industry spillovers and (iii) inter......-industry linkages. We do so by exploiting a unique data set covering the universe of manufacturing firms in Denmark for the period 1995–2006 which combines transaction-level export data, firm accounting data, employer–employee linked data and information from yearly input–output tables. We corroborate...... the literature on export spillovers by presenting robust evidence of destination-specific export spillovers. The results suggest that labour mobility as well as intra- and inter-industry linkages (backward linkages) are important channels for export spillovers, while presenting heterogeneous effects across firms...

  14. GTP-binding proteins in rat liver nuclear envelopes

    International Nuclear Information System (INIS)

    Rubins, J.B.; Benditt, J.O.; Dickey, B.F.; Riedel, N.

    1990-01-01

    Nuclear transport as well as reassembly of the nuclear envelope (NE) after completion of mitosis are processes that have been shown to require GTP and ATP. To study the presence and localization of GTP-binding proteins in the NE, we have combined complementary techniques of [alpha-32P]GTP binding to Western-blotted proteins and UV crosslinking of [alpha-32P]GTP with well-established procedures for NE subfractionation. GTP binding to blotted NE proteins revealed five low molecular mass GTP-binding proteins of 26, 25, 24.5, 24, and 23 kDa, and [alpha-32P]GTP photoaffinity labeling revealed major proteins with apparent molecular masses of 140, 53, 47, 33, and 31 kDa. All GTP-binding proteins appear to localize preferentially to the inner nuclear membrane, possibly to the interface between inner nuclear membrane and lamina. Despite the evolutionary conservation between the NE and the rough endoplasmic reticulum, the GTP-binding proteins identified differed between these two compartments. Most notably, the 68- and 30-kDa GTP-binding subunits of the signal recognition particle receptor, which photolabeled with [alpha-32P]GTP in the rough endoplasmic reticulum fraction, were totally excluded from the NE fraction. Conversely, a major 53-kDa photolabeled protein in the NE was absent from rough endoplasmic reticulum. Whereas Western-blotted NE proteins bound GTP specifically, all [alpha-32P]GTP photolabeled proteins could be blocked by competition with ATP, although with a competition profile that differed from that obtained with GTP. In comparative crosslinking studies with [alpha-32P]ATP, we have identified three specific ATP-binding proteins with molecular masses of 160, 78, and 74 kDa. The localization of GTP- and ATP-binding proteins within the NE appears appropriate for their involvement in nuclear transport and in the GTP-dependent fusion of nuclear membranes

  15. A Human Nuclear Shuttling Protein That Interacts with Human Immunodeficiency Virus Type 1 Matrix Is Packaged into Virions

    Science.gov (United States)

    Gupta, Kalpana; Ott, David; Hope, Thomas J.; Siliciano, Robert F.; Boeke, Jef D.

    2000-01-01

    Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55Gag and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4+ T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55Gag and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport. PMID:11090181

  16. Export strategy

    DEFF Research Database (Denmark)

    Knudsen, Thorbjørn; Koed Madsen, Tage

    2002-01-01

    It is argued here that traditional export strategy research (encompassing the study of internationalization processes and export performance) is characterized by weak theoretical foundations and could benefit from a reorientation towards a dynamic capabilities perspective (DCP). We seek to draw...... on insights from DCP in order to devise a theoretical basis that could enrich export strategy research. Although our development of DCP insights builds on previous work, it also adds a crucial distinction between knowledge stocks and informational architecture. Changes in architecture are of greater...... importance. Following this elaboration of the dynamic capabilities perspective, we outline some implications and guidelines for future export strategy research....

  17. Studies with GFP-Vpr fusion proteins: induction of apoptosis but ablation of cell-cycle arrest despite nuclear membrane or nuclear localization

    International Nuclear Information System (INIS)

    Waldhuber, Megan G.; Bateson, Michael; Tan, Judith; Greenway, Alison L.; McPhee, Dale A.

    2003-01-01

    The human immunodeficiency virus type 1 (HIV-1) Vpr protein is known to arrest the cell cycle in G 2 /M and induce apoptosis following arrest. The functions of Vpr relative to its location in the cell remain unresolved. We now demonstrate that the location and function of Vpr are dependent on the makeup of fusion proteins and that the functions of G 2 /M arrest and apoptosis are separable. Using green fluorescence protein mutants (EGFP or EYFP), we found that fusion at either the N- or C-terminus compromised the ability of Vpr to arrest cell cycling, relative to that of His-Vpr or wild-type protein. Additionally, utilizing the ability to specifically identify cells expressing the fusion proteins, we confirm that Vpr can induce apoptosis, but appears to be independent of cell-cycle arrest in G 2 /M. Both N- and C-terminal Vpr/EYFP fusion proteins induced apoptosis but caused minimal G 2 /M arrest. These studies with Vpr fusion proteins indicate that the functions of Vpr leading to G 2 /M arrest and apoptosis are separable and that fusion of Vpr to EGFP or EYFP affected the localization of the protein. Our findings suggest that nuclear membrane localization and nuclear import and export are strongly governed by modification of the N-terminus of Vpr

  18. A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism.

    Science.gov (United States)

    Visootsat, Akasit; Payungporn, Sunchai; T-Thienprasert, Nattanan P

    2015-12-01

    Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.

  19. Diffusion and export dynamics of 137Cs deposited on the forested area in Fukushima after the nuclear power plant accident in March 2011. Preliminary results

    International Nuclear Information System (INIS)

    Ohte, Nobuhito; Iseda, Kohei; Tanoi, Keitaro; Murakami, Masashi; Suzuki, Takahiro; Ishii, Nobuyoshi

    2012-01-01

    A massive amount of radioactive substances, including cesium-137 ( 137 Cs), emitted from the disabled nuclear power plant, has been deposited on the forested areas in the northeastern region of Honshu Island, Japan after the Fukushima Daiichi nuclear power plant accident. Forests in these regions are particularly important, not only for the forest products industry but also for source areas of drinking water and for residential environments. To clarify the mechanisms of diffusion and export of 137 Cs deposited on the forested ecosystem, we initiated intensive field observations in a small catchment that included forest and farmlands. Specifically, we were interested in the Kami-Oguni River catchment that is located in the northern part of Fukushima Prefecture. The following expected major pathways of 137 Cs export and diffusion were investigated: 1) transportation of dissolved and particulate or colloidal forms via hydrological processes within a forested catchment and export dynamics through the stream, and 2) diffusion through the food web in terrestrial and aquatic ecosystems of forests. Preliminary findings indicated the following: 1) Most of the 137 Cs was discharged as suspended matter. High water flow generated by storm acted to accelerate the transportation of 137 Cs from the forested catchments. Thus, the estimation of 137 Cs export requires precise evaluation of the high flow acceleration during storm events; 2) Because litter and its detritus may form the biggest pool of 137 Cs in the forested ecosystem, 137 Cs diffusion occurs more rapidly through the detritus food chain than the grazing food chain. Most predators have already ingested 137 Cs, particularly in aquatic environments. An urgent question that needs to be addressed is when and how 137 Cs diffuses through grazing food chains and how rapidly this process occurs. To elucidate or to be able to predict these phenomena, the mechanisms of 137 Cs release from litter and soil's organic matter

  20. Touchstone for Japan's Export of nuclear power plant system. Vinh Hai unit 1 and 2 project in the Ninh Thuan province in Viet Nam

    International Nuclear Information System (INIS)

    Mitsumata, Hiroki; Takekuro, Ichiro; Kaneko, Kumao; Suzuki, Hideaki; Saito, Shinzo

    2011-01-01

    'Japan-Viet Nam Joint Statement on the Strategic Partnership for Peace and Prosperity in Asia' issued after the meeting between Japan-Viet Nam Prime Ministers on October 31, affirmed that the Vietnamese Government had decided to choose Japan as the cooperation partner for building Vinh Hai Unit 1 and 2 Project in the Ninh Thuan Province, southern Viet Nam, which showed substantially an order of Japan was arranged informally. 'International Nuclear Energy Development of Japan Co., Ltd. (JINED)' set up by industry and government, would negotiate to decide fundamental parameters such as type and power of nuclear power plants with the start of operation scheduled in 2021. This special issue consisted of six articles on significance of the project of Japan's first export, feasibility studies and future perspective and regional effects with introduction of nuclear power station in Viet Nam. (T. Tanaka)

  1. Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

    International Nuclear Information System (INIS)

    Lloyd, Richard E.

    2015-01-01

    Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups. - Highlights: • Nuclear shuttling host proteins are commonly hijacked by RNA viruses to support replication. • A limited group of ubiquitous RNA binding proteins are commonly hijacked by a broad range of viruses. • Key virus proteins alter roles of RNA binding proteins in different stages of virus replication

  2. Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

    Energy Technology Data Exchange (ETDEWEB)

    Lloyd, Richard E., E-mail: rlloyd@bcm.edu

    2015-05-15

    Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups. - Highlights: • Nuclear shuttling host proteins are commonly hijacked by RNA viruses to support replication. • A limited group of ubiquitous RNA binding proteins are commonly hijacked by a broad range of viruses. • Key virus proteins alter roles of RNA binding proteins in different stages of virus replication.

  3. Communications of 15 November 1999 received from Member States regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the letters dated 15 November 1999 received by the Director General of the IAEA from the Resident Representatives of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Luxembourg, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom, and the United States of America, concerning the export of nuclear material and of certain categories of equipment and other material

  4. Communication received from the Permanent Mission of Denmark to the Agency regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2007-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology

  5. Communications of 17 October 1996 received from Member States regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1999-01-01

    The document reproduces the text of the letter received by the Director General of the IAEA on 17 October 1996 from the Resident Representatives of Argentina, Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, the United Kingdom, and the United States of America, concerning the export of nuclear materials and of certain categories of equipment and other material

  6. Communication received from the Permanent Mission of Denmark to the Agency regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2007-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology [es

  7. Exporting nuclear wastes to Russia: how Greenpeace contributed to make a traffic stop which has been lasting for nearly 40 years

    International Nuclear Information System (INIS)

    2010-01-01

    After having recalled how Greenpeace discovered the existence of contracts between the French CEA (and later AREVA) and Russia for the export of nuclear wastes to Russia, this document specifies which kinds of wastes are concerned: depleted uranium (from the EURODIF plant in Tricastin) and reprocessed uranium (from La Hague). It briefly reports the different actions performed by Greenpeace about this trade which occurred against the Russian law on the protection of the environment and against a European directive. It finally denounces the posture and statements of AREVA about a possible use of these wastes

  8. Communication of 30 June 1995 Received from France Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania [ru

  9. Communication of 30 June 1995 Received from France Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1995-01-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania [es

  10. Communication of 30 June 1995 Received from France Regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1995-01-01

    The Director General has received letters concerning the export of nuclear material and of certain categories of equipment and other material from the following Resident Representatives to the International Atomic Energy Agency: a letter dated 28 February 1994 from the Resident Representative of France; letters dated 1 March 1994 from the Resident Representatives of Australia, Austria, Bulgaria, Canada, the Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Ireland, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom of Great Britain and Northern Ireland, and the United States of America; and a letter dated 22 March 1994 from the Resident Representative of Romania

  11. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology. Nuclear Transfers and Nuclear-Related Dual-Use Transfers

    International Nuclear Information System (INIS)

    1993-04-01

    The Director General has received a Note Verbale dated 5 March 1993 from the Ministry of Foreign Affairs of the Slovak Republic. The purpose of the Note Verbale is to provide information on that Governments' guidelines for Nuclear Transfers and for Transfers of of Nuclear-related Dual-use Equipment, Material and Related Technology. In the light of the wish expressed at the end of each Note Verbale, the text of the Note Verbale is annexed hereto [fr

  12. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology. Nuclear Transfers and Nuclear-Related Dual-Use Transfers

    International Nuclear Information System (INIS)

    1993-04-01

    The Director General has received a Note Ver bale dated 5 March 1993 from the Ministry of Foreign Affairs of the Slovak Republic. The purpose of the Note Ver bale is to provide information on that Governments' guidelines for Nuclear Transfers and for Transfers of of Nuclear-related Dual-use Equipment, Material and Related Technology. In the light of the wish expressed at the end of each Note Ver bale, the text of the Note Ver bale is annexed hereto

  13. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology. Nuclear Transfers and Nuclear-Related Dual-Use Transfers

    International Nuclear Information System (INIS)

    1993-04-01

    The Director General has received a Note Verbale dated 5 March 1993 from the Ministry of Foreign Affairs of the Slovak Republic. The purpose of the Note Verbale is to provide information on that Governments' guidelines for Nuclear Transfers and for Transfers of of Nuclear-related Dual-use Equipment, Material and Related Technology. In the light of the wish expressed at the end of each Note Verbale, the text of the Note Verbale is annexed hereto [es

  14. Identification and characterization of proteins involved in nuclear organization using Drosophila GFP protein trap lines.

    Directory of Open Access Journals (Sweden)

    Margaret Rohrbaugh

    Full Text Available Strains from a collection of Drosophila GFP protein trap lines express GFP in the normal tissues where the endogenous protein is present. This collection can be used to screen for proteins distributed in the nucleus in a non-uniform pattern.We analyzed four lines that show peripheral or punctate nuclear staining. One of these lines affects an uncharacterized gene named CG11138. The CG11138 protein shows a punctate distribution in the nuclear periphery similar to that of Drosophila insulator proteins but does not co-localize with known insulators. Interestingly, mutations in Lamin proteins result in alterations in CG11138 localization, suggesting that this protein may be a novel component of the nuclear lamina. A second line affects the Decondensation factor 31 (Df31 gene, which encodes a protein with a unique nuclear distribution that appears to segment the nucleus into four different compartments. The X-chromosome of males is confined to one of these compartments. We also find that Drosophila Nucleoplasmin (dNlp is present in regions of active transcription. Heat shock leads to loss of dNlp from previously transcribed regions of polytene chromosome without redistribution to the heat shock genes. Analysis of Stonewall (Stwl, a protein previously found to be necessary for the maintenance of germline stem cells, shows that Stwl is present in a punctate pattern in the nucleus that partially overlaps with that of known insulator proteins. Finally we show that Stwl, dNlp, and Df31 form part of a highly interactive network. The properties of other components of this network may help understand the role of these proteins in nuclear biology.These results establish screening of GFP protein trap alleles as a strategy to identify factors with novel cellular functions. Information gained from the analysis of CG11138 Stwl, dNlp, and Df31 sets the stage for future studies of these proteins.

  15. Organizing export strategies.

    OpenAIRE

    G. Lojacono; M. Venzin

    2014-01-01

    The article unfolds as follows: after a brief introduction on the relevance of international trade and the characteristics of export strategies, we describe four distinct archetypes: export manager, centralistic export developer, export skimmer, integrated export developer.

  16. Communication received from the Member States of the European Community regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1992-12-01

    The document reproduces the text of the note verbale received by the Director General on 30 November 1992 from the Permanent Missions to the Agency of Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain and the United Kingdom of Great Britain and Northern Ireland, relating to the provision of certain additional information on production, inventories and international transfer of nuclear material and on exports of certain relevant equipment and non-nuclear material. The note verbale dated 23 November 1992, received by the Director General from the Commission of the European Communities and relating to the same subject, is reproduced as well

  17. Early localization of NPA58, a rat nuclear pore-associated protein

    Indian Academy of Sciences (India)

    We have studied the mitotic reassembly of the nuclear envelope, using antibodies to nuclear marker proteins and NPA58 in F-111 rat fibroblast cells. In earlier studies we have proposed that NPA58, a 58 kDa rat nuclear protein, is involved in nuclear protein import. In this report, NPA58 is shown to be localized on the ...

  18. High-resolution nuclear magnetic resonance studies of proteins.

    Science.gov (United States)

    Jonas, Jiri

    2002-03-25

    The combination of advanced high-resolution nuclear magnetic resonance (NMR) techniques with high-pressure capability represents a powerful experimental tool in studies of protein folding. This review is organized as follows: after a general introduction of high-pressure, high-resolution NMR spectroscopy of proteins, the experimental part deals with instrumentation. The main section of the review is devoted to NMR studies of reversible pressure unfolding of proteins with special emphasis on pressure-assisted cold denaturation and the detection of folding intermediates. Recent studies investigating local perturbations in proteins and the experiments following the effects of point mutations on pressure stability of proteins are also discussed. Ribonuclease A, lysozyme, ubiquitin, apomyoglobin, alpha-lactalbumin and troponin C were the model proteins investigated.

  19. In vitro nuclear interactome of the HIV-1 Tat protein.

    LENUS (Irish Health Repository)

    Gautier, Virginie W

    2009-01-01

    BACKGROUND: One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86-101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry. RESULTS: Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied in silico analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture. CONCLUSION: We have completed the in vitro Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will

  20. CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

    Science.gov (United States)

    Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

    2016-08-01

    Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

  1. Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites

    DEFF Research Database (Denmark)

    Sleebs, Brad E; Lopaticki, Sash; Marapana, Danushka S

    2014-01-01

    , Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed...... surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp....... and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target....

  2. Diffusion and export dynamics of "1"3"7Cs deposited on the forested area in Fukushima after the nuclear power plant accident in March 2011. Preliminary results

    International Nuclear Information System (INIS)

    Ohte, Nobuhito; Iseda, Kohei; Tanoi, Keitaro; Murakami, Masashi; Suzuki, Takahiro; Ishii, Nobuyoshi

    2013-01-01

    A massive amount of radioactive substances, including cesium-137 ("1"3"7Cs), emitted from the disabled nuclear power plant, has been deposited on the forested areas in the northeastern region of Honshu Island, Japan after the Fukushima Daiichi nuclear power plant accident. Forests in these regions are particularly important, not only for the forest products industry but also for source areas of drinking water and for residential environments. To clarify the mechanisms of diffusion and export of "1"3"7Cs deposited on the forested ecosystem, we initiated intensive field observations in a small catchment that included forest and farmlands. Specifically, we were interested in the Kami-Oguni River catchment that is located in the northern part of Fukushima Prefecture. The following expected major pathways of "1"3"7Cs export and diffusion were investigated: 1) transportation of dissolved and particulate or colloidal forms via hydrological processes within a forested catchment and export dynamics through the stream, and 2) diffusion through the food web in terrestrial and aquatic ecosystems of forests. Preliminary findings indicated the following: 1) Most of the "1"3"7Cs was discharged as suspended matter. High water flow generated by storm acted to accelerate the transportation of "1"3"7Cs from the forested catchments. Thus, the estimation of "1"3"7Cs export requires precise evaluation of the high flow acceleration during storm events; 2) Because litter and its detritus may form the biggest pool of "1"3"7Cs in the forested ecosystem, "1"3"7Cs diffusion occurs more rapidly through the detritus food chain than the grazing food chain. Most predators have already ingested "1"3"7Cs, particularly in aquatic environments. An urgent question that needs to be addressed is when and how "1"3"7Cs diffuses through grazing food chains and how rapidly this process occurs. To elucidate or to be able to predict these phenomena, the mechanisms of "1"3"7Cs release from litter and soil

  3. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Directory of Open Access Journals (Sweden)

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  4. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    Science.gov (United States)

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

  5. Dynamic nuclear polarization of membrane proteins: covalently bound spin-labels at protein–protein interfaces

    International Nuclear Information System (INIS)

    Wylie, Benjamin J.; Dzikovski, Boris G.; Pawsey, Shane; Caporini, Marc; Rosay, Melanie; Freed, Jack H.; McDermott, Ann E.

    2015-01-01

    We demonstrate that dynamic nuclear polarization of membrane proteins in lipid bilayers may be achieved using a novel polarizing agent: pairs of spin labels covalently bound to a protein of interest interacting at an intermolecular interaction surface. For gramicidin A, nitroxide tags attached to the N-terminal intermolecular interface region become proximal only when bimolecular channels forms in the membrane. We obtained signal enhancements of sixfold for the dimeric protein. The enhancement effect was comparable to that of a doubly tagged sample of gramicidin C, with intramolecular spin pairs. This approach could be a powerful and selective means for signal enhancement in membrane proteins, and for recognizing intermolecular interfaces

  6. Communications received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-04-01

    The document reproduces the text of a Note Verbale dated 5 March 1993 received by the Director General from the Ministry of Foreign Affairs of the Slovak Republic, in order to provide information on that Government's Guidelines for Nuclear Transfer and for Transfers of Nuclear - Related Dual-Use Equipment, Material and Related Technology

  7. 10 CFR 73.73 - Requirement for advance notice and protection of export shipments of special nuclear material of...

    Science.gov (United States)

    2010-01-01

    ... shipments of special nuclear material of low strategic significance. 73.73 Section 73.73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Records and Reports § 73.73... Incident Response, using any appropriate method listed in § 73.4; (2) Assure that the notification will be...

  8. Fluoride export (FEX) proteins from fungi, plants and animals are 'single barreled' channels containing one functional and one vestigial ion pore

    Science.gov (United States)

    Berbasova, Tetyana; Nallur, Sunitha; Sells, Taylor; Smith, Kathryn D.; Gordon, Patricia B.; Tausta, Susan Lori

    2017-01-01

    The fluoride export protein (FEX) in yeast and other fungi provides tolerance to fluoride (F-), an environmentally ubiquitous anion. FEX efficiently eliminates intracellular fluoride that otherwise would accumulate at toxic concentrations. The FEX homolog in bacteria, Fluc, is a ‘double-barreled’ channel formed by dimerization of two identical or similar subunits. FEX in yeast and other eukaryotes is a monomer resulting from covalent fusion of the two subunits. As a result, both potential fluoride pores are created from different parts of the same protein. Here we identify FEX proteins from two multicellular eukaryotes, a plant Arabidopsis thaliana and an animal Amphimedon queenslandica, by demonstrating significant fluoride tolerance when these proteins are heterologously expressed in the yeast Saccharomyces cerevisiae. Residues important for eukaryotic FEX function were determined by phylogenetic sequence alignment and functional analysis using a yeast growth assay. Key residues of the fluoride channel are conserved in only one of the two potential fluoride-transporting pores. FEX activity is abolished upon mutation of residues in this conserved pore, suggesting that only one of the pores is functional. The same topology is conserved for the newly identified FEX proteins from plant and animal. These data suggest that FEX family of fluoride channels in eukaryotes are ‘single-barreled’ transporters containing one functional pore and a second non-functional vestigial remnant of a homologous gene fusion event. PMID:28472134

  9. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, So Young; Park, Ji Hoon [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of); Kim, Young Ho; Kang, Jong Seong [College of Pharmacy, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Min, Ji-Young, E-mail: jiyoung.min@ip-korea.org [Respiratory Viruses Research Laboratory, Discovery Biology Department, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400 (Korea, Republic of)

    2016-03-04

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  10. A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein

    International Nuclear Information System (INIS)

    Chang, So Young; Park, Ji Hoon; Kim, Young Ho; Kang, Jong Seong; Min, Ji-Young

    2016-01-01

    The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug-resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl-β-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose-dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. - Highlights: • The plant-derived natural product TGBG has broad-spectrum antiviral activity against seasonal influenza A and B viruses. • TGBG has a novel anti-viral mechanism of action that from differs from the currently available anti-influenza drugs. • TGBG hinders nuclear export of the influenza virus ribonucleoprotein (v

  11. Autoradiographic study of nuclear protein acetylation during Locust spermiogenesis

    International Nuclear Information System (INIS)

    Bouvier, D.; Chevaillier, P.

    1975-01-01

    Autoradiographic studies, at the light and electron microscope level, demonstrate that spermatid nuclei of the Locust Locusta migratoria incorporate 3 H-acetate, especially during the first stages of spermiogenesis. The highest level of acetate incorporation is observed during stage II of spermiogenesis. During this stage and the following, the spermatid nucleus undergoes a number of structural and chemical modifications: chromatin decondenses and somatic histones are progressively replaced by newly synthesized arginine-rich proteins. Therefore, the higher degree of acetylation of nuclear components coincides with chromatin decondensation and precedes the protein transition occurring in later stages. Cytochemical and autoradiographic tests have been realized so as to localize 3 H-acetate in the nuclear components. Trichloracetic acid was used at various concentrations: the action of hydrochloric acid, pronase and DNase was also tested. The results support the idea that proteins, and among them histones, are the only nuclear components to be acetylated during spermiogenesis. Thus, histone acetylation seems to play an important role in modulating histone-DNA interactions and allowing histone replacement [fr

  12. Communication from the Permanent Mission of the Russian Federation to the International Atomic Energy Agency regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of a letter received by the Director general of the IAEA from Permanent Mission of the Russian Federation to the International Atomic Energy Agency concerning the export of nuclear material and of certain categories of equipment and other material

  13. Communication of 29 April 1996 received from the Permanent Mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-06-07

    The document contains the text of a note verbale dated 29 April 1996 received by the Director General of IAEA from the Permanent Mission of the Russian Federation which provides information on the export policies and practices of the Government of the Russian Federation with respect to transfer of nuclear-related dual-use equipment, material and related technology.

  14. Communication of 29 April 1996 received from the Permanent Mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1996-01-01

    The document contains the text of a note verbale dated 29 April 1996 received by the Director General of IAEA from the Permanent Mission of the Russian Federation which provides information on the export policies and practices of the Government of the Russian Federation with respect to transfer of nuclear-related dual-use equipment, material and related technology

  15. Nuclear importation, exportation and production within the framework of the law of the communities or zones of integration

    International Nuclear Information System (INIS)

    Bertone, L.

    1986-01-01

    The article starts from the hypothesis that a harmonisation of regulations concerning the international commerce of nuclear technology would be more useful, if in a first period it is managed on the level of communities (Euratom) or integration zones (ALADI). European and South-American regulations as well as certain aspects of the North-South-cooperation are presented. As yet, a universal cooperation in the field of nuclear material is refused. (CW) [de

  16. Protein Sub-Nuclear Localization Prediction Using SVM and Pfam Domain Information

    Science.gov (United States)

    Kumar, Ravindra; Jain, Sohni; Kumari, Bandana; Kumar, Manish

    2014-01-01

    The nucleus is the largest and the highly organized organelle of eukaryotic cells. Within nucleus exist a number of pseudo-compartments, which are not separated by any membrane, yet each of them contains only a specific set of proteins. Understanding protein sub-nuclear localization can hence be an important step towards understanding biological functions of the nucleus. Here we have described a method, SubNucPred developed by us for predicting the sub-nuclear localization of proteins. This method predicts protein localization for 10 different sub-nuclear locations sequentially by combining presence or absence of unique Pfam domain and amino acid composition based SVM model. The prediction accuracy during leave-one-out cross-validation for centromeric proteins was 85.05%, for chromosomal proteins 76.85%, for nuclear speckle proteins 81.27%, for nucleolar proteins 81.79%, for nuclear envelope proteins 79.37%, for nuclear matrix proteins 77.78%, for nucleoplasm proteins 76.98%, for nuclear pore complex proteins 88.89%, for PML body proteins 75.40% and for telomeric proteins it was 83.33%. Comparison with other reported methods showed that SubNucPred performs better than existing methods. A web-server for predicting protein sub-nuclear localization named SubNucPred has been established at http://14.139.227.92/mkumar/subnucpred/. Standalone version of SubNucPred can also be downloaded from the web-server. PMID:24897370

  17. The European atomic politics under the treaty of Lisboa and actual questions of the export of nuclear waste

    International Nuclear Information System (INIS)

    Ehlenz, Christian; Frenz, Walter

    2011-01-01

    In the context of the actual discussion considerably influenced by safety questions activated by the reactor accident in Tschernobyl in 1986, the EAG gains increasing significance. However, a substantial safety risk proceeds not only with nuclear power stations as a possible goal for attacks of terror, but also from the uncontrolled spreading with nuclear material. The latter equally affects the question on handling radioactive waste materials being straightly discussed in Germany as well as in the European Union as proven by the European Union commissioner Oettinger. This is to be considered in connection with the problem how extensively the competences of the Euratom for the nuclear safety may be interpreted. The actual changes of the legal situation by means of the Lisboa contract for the EAG altogether turned out marginally and let its demand for a reform based on the actual conditions appear more urgent.

  18. Export-defective lamB protein is a target for translational control caused by ompC porin overexpression.

    OpenAIRE

    Click, E M; Schnaitman, C A

    1989-01-01

    Overexpression of OmpC protein from an inducible plasmid vector reduced the amount of the precursor form of LamB protein in LamB signal sequence mutants. The stability of the precursor form of LamB protein was not affected, indicating that the effect of OmpC overexpression was on the synthesis of the precursor rather than on degradation. These results indicate that a functional signal sequence is not required on an outer membrane protein for it to be a target for translational control.

  19. Distinct roles for key karyogamy proteins during yeast nuclear fusion.

    Science.gov (United States)

    Melloy, Patricia; Shen, Shu; White, Erin; Rose, Mark D

    2009-09-01

    During yeast mating, cell fusion is followed by the congression and fusion of the two nuclei. Proteins required for nuclear fusion are found at the surface (Prm3p) and within the lumen (Kar2p, Kar5p, and Kar8p) of the nuclear envelope (NE). Electron tomography (ET) of zygotes revealed that mutations in these proteins block nuclear fusion with different morphologies, suggesting that they act in different steps of fusion. Specifically, prm3 zygotes were blocked before formation of membrane bridges, whereas kar2, kar5, and kar8 zygotes frequently contained them. Membrane bridges were significantly larger and occurred more frequently in kar2 and kar8, than in kar5 mutant zygotes. The kinetics of NE fusion in prm3, kar5, and kar8 mutants, measured by live-cell fluorescence microscopy, were well correlated with the size and frequency of bridges observed by ET. However the kar2 mutant was defective for transfer of NE lumenal GFP, but not diffusion within the lumen, suggesting that transfer was blocked at the NE fusion junction. These observations suggest that Prm3p acts before initiation of outer NE fusion, Kar5p may help dilation of the initial fusion pore, and Kar2p and Kar8p act after outer NE fusion, during inner NE fusion.

  20. Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

    Science.gov (United States)

    Copeland, Anna Maria; Van Deusen, Nicole M; Schmaljohn, Connie S

    2015-12-01

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon. Published by Elsevier Inc.

  1. Some problems of recent 'All Japan' strategy for nuclear power exports. Identification of its problems and a proposal for improvement based on international development strategies of the major three categories of businesses constituting nuclear power industry

    International Nuclear Information System (INIS)

    Tanabe, Tomoyuki

    2011-01-01

    In Japan, 'All Japan' strategy for nuclear power exports, which arranges engineering companies and electric utilities to sell nuclear power plants providing engineering, procurement, construction and operation abroad, with governmental support of expanded trade insurance, is strongly promoted today as a part of Japan's national growth strategy. However, 'All Japan' strategy generates some problems because the strategy does not consider difference of business strategies concerning international development of each enterprise. This report identifies problems of 'All Japan' strategy based on environmental scanning of major three categories of businesses, which are big nuclear technology companies, vendors and electric utilities constituting nuclear power industry. And this report proposes the way to improve the strategy as follows to resolve those problems. 1) It is necessary to assess the risk of the project that is to be undertaken by 'All Japan' approach carefully. 2) Governmental support for vendors is also needed because the vendors are source of strength of international development of the nuclear industry in Japan. 3) Where the cooperation among the electric utilities is necessary, imposing the risk burden on the utilities should be avoided. 4) It is necessary for government to take measures about 'Weakness' and 'Threat' that each category of business commonly faces. (author)

  2. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.

    LENUS (Irish Health Repository)

    Gu, Lili

    2011-03-14

    Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  3. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

    Directory of Open Access Journals (Sweden)

    Sheehy Noreen

    2011-03-01

    Full Text Available Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  4. Uranium enrichment export control guide: Gaseous diffusion

    Energy Technology Data Exchange (ETDEWEB)

    1989-09-01

    This document was prepared to serve as a guide for export control officials in their interpretation, understanding, and implementation of export laws that relate to the Zangger International Trigger List for gaseous diffusion uranium enrichment process components, equipment, and materials. Particular emphasis is focused on items that are especially designed or prepared since export controls are required for these by States that are party to the International Nuclear Nonproliferation Treaty.

  5. Communication received from Members regarding Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1984-02-01

    The Director General has received letters from the Resident Representatives to the Agency of the following Member States concerning the commitments of these Member States under Article III, paragraph 2, of the Treaty on the Non-Proliferation of Nuclear Weapons (the date of each letter is given in parentheses after the name of the Member State:

  6. Communications Received from Members Regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1986-02-01

    The Director General has received a letter dated 28 January 1986 from the Permanent Representative of Hungary to the Agency concerning the commitments of Hungary under Article III, paragraph 2, of the Treaty on the Non-Proliferation of Nuclear Weapons

  7. Communications Received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1978-12-01

    On 1 September 1978 the Director General received similar letters of that date from the Resident Representatives of Poland and the German Democratic Republic to the Agency relating to the commitments of these Members under Article III, paragraph 2, of the Treaty on the Non- Proliferation of Nuclear Weapons

  8. Prm3p is a pheromone-induced peripheral nuclear envelope protein required for yeast nuclear fusion.

    Science.gov (United States)

    Shen, Shu; Tobery, Cynthia E; Rose, Mark D

    2009-05-01

    Nuclear membrane fusion is the last step in the mating pathway of the yeast Saccharomyces cerevisiae. We adapted a bioinformatics approach to identify putative pheromone-induced membrane proteins potentially required for nuclear membrane fusion. One protein, Prm3p, was found to be required for nuclear membrane fusion; disruption of PRM3 caused a strong bilateral defect, in which nuclear congression was completed but fusion did not occur. Prm3p was localized to the nuclear envelope in pheromone-responding cells, with significant colocalization with the spindle pole body in zygotes. A previous report, using a truncated protein, claimed that Prm3p is localized to the inner nuclear envelope. Based on biochemistry, immunoelectron microscopy and live cell microscopy, we find that functional Prm3p is a peripheral membrane protein exposed on the cytoplasmic face of the outer nuclear envelope. In support of this, mutations in a putative nuclear localization sequence had no effect on full-length protein function or localization. In contrast, point mutations and deletions in the highly conserved hydrophobic carboxy-terminal domain disrupted both protein function and localization. Genetic analysis, colocalization, and biochemical experiments indicate that Prm3p interacts directly with Kar5p, suggesting that nuclear membrane fusion is mediated by a protein complex.

  9. Intracellular trafficking of LET-756, a fibroblast growth factor of C. elegans, is controlled by a balance of export and nuclear signals

    International Nuclear Information System (INIS)

    Popovici, Cornel; Fallet, Mathieu; Marguet, Didier; Birnbaum, Daniel; Roubin, Regine

    2006-01-01

    The superfamily of fibroblast growth factors (FGF), which counts 22 members in humans, exerts many functions during animal development and adult life. LET-756 is one of the two FGFs of the nematode C. elegans. Re-introduction of LET-756 in a null mutant strain restores viability, allowing the study of structural requirements for LET-756 trafficking and function. LET-756 protein has several regions and motifs, including a non-classical internal motif required for secretion. We show here that a main difference in the wild-type LET-756 molecule and a truncated molecule that mimics a partial loss-of-function mutant lies on subnuclear expression. Using Cos-1 cells and rescue activity we show that: (i) nuclear localization is due to various redundant NLS, one of them acting as a nucleolar localization signal; (ii) nuclear LET-756 is addressed to the speckles by a stretch of glutamine residues; (iii) nuclear LET-756 is trafficking between speckles and nucleoli; (iv) in the nucleolus, LET-756 is associated with proteins of the rRNA splicing compartment; (v) changing LET-756 secretion signal prevents its nuclear localization. We propose that LET-756 exerts its functions through a balance between secreted and nuclear forms due to two opposite addressing signals (i) synergy of several NLS and (ii) attenuated secretion signal

  10. Phosphorylation near nuclear localization signal regulates nuclear import of adenomatous polyposis coli protein

    OpenAIRE

    Zhang, Fang; White, Raymond L.; Neufeld, Kristi L.

    2000-01-01

    Mutation of the adenomatous polyposis coli (APC) gene is an early step in the development of colorectal carcinomas. APC protein is located in both the cytoplasm and the nucleus. The objective of this study was to define the nuclear localization signals (NLSs) in APC protein. APC contains two potential NLSs comprising amino acids 1767–1772 (NLS1APC) and 2048–2053 (NLS2APC). Both APC NLSs are well conserved among human, mouse, rat, and fly. NLS1APC and NLS2APC each w...

  11. Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates corticotropin-releasing hormone expression

    NARCIS (Netherlands)

    Zhou, Tian; Wang, Shanshan; Ren, Haigang; Qi, Xin-Rui; Luchetti, Sabina; Kamphuis, Willem; Zhou, Jiang-Ning; Wang, Guanghui; Swaab, Dick F.

    2010-01-01

    The recently discovered dendritic cell nuclear protein-1 is the product of a novel candidate gene for major depression. The A allele encodes full-length dendritic cell nuclear protein-1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5. In the

  12. Binding of triiodothyronine to rat liver nuclear matrix. influence of thyroid hormones on the phosphorylation of nuclear matrix proteins

    International Nuclear Information System (INIS)

    Adylova, A.T.; Atakhanova, B.A.

    1986-01-01

    The interaction of thyroid hormones with rat liver nuclear matrix proteins was investigated. It was shown that the nuclear matrix contains sites that bind triiodothyronine with high affinity (K = 1.07.10 9 M -1 ) and limited capacity (the maximum binding capacity is equal to 28 /SUP a/ .5 fmoles of triiodothyronine per 100 ug protein). Electrophoretic identification of the matrix proteins that bind triiodothyronine was performed. The molecular weight of the main triiodothyronine-binding fraction is 50,000-52,000. It was shown that the administration of triiodothyronine to thyroidectomized rats stimulates the phosphorylation of all the protein fractions of the nuclear matrix

  13. Export insurance

    International Nuclear Information System (INIS)

    1981-01-01

    These notes are intended as a general guide for the use of members of the Canadian Nuclear Association who are, or may become, involved in supplying goods or services or contracting/ erecting as part of a contract to supply a nuclear facility to an overseas country. They give information to the type of insurances needed and available, the parties normally responsible for providing the coverages, the intent and operation of the various policies, general methods of charging premiums, and main exclusions

  14. Communications Received from Members Regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1990-11-01

    The Director General has received letters dated 3 September 1990 from the Resident Representatives to the Agency of Australia, Canada, Czechoslovakia, Denmark, Finland, the German Democratic Republic, the Federal Republic of Germany, Greece, Hungary, Ireland, Japan, Luxembourg, the Netherlands, Norway, Poland, Sweden, the Union of Soviet Socialist Republics, the United Kingdom of Great Britain and Northern Ireland, and the United States of America concerning the commitments of these Member States under Article III, paragraph 2, of the Treaty on the Non-Proliferation of Nuclear Weapons

  15. Competitiveness, export control and export promotion of dual-use goods. European and German balancing exercises

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2014-01-01

    The EU Commission Communication of 24 April 2014 to the Council and the European Parliament ''The review of export control policy: Ensuring Security and Competitiveness in a changing world'' as well as the increasingly number of inquiries and applications to the German Federal Government (e.g. the rejection of Hermes guarantees and state funding of nuclear export and termination of bilateral cooperation in the field of nuclear technologies) once again reason to discuss the current tension between the principle of free movement of goods, competitiveness and export promotion on the one hand and the export control on the other.

  16. Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

    2015-12-15

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Rift Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.

  17. Early localization of NPA58, a rat nuclear pore-associated protein, to ...

    Indian Academy of Sciences (India)

    Unknown

    Mitotic reassembly; nuclear envelope assembly; nuclear pore complex ... A consensus model for the vertebrate NPC based on ... A mouse monoclonal antibody to PCNA (PC10) a protein associ- ated with DNA replication centres during S ...

  18. Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.

    Science.gov (United States)

    Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki

    2017-06-01

    Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

  19. Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export.

    Science.gov (United States)

    Krebber, H; Taura, T; Lee, M S; Silver, P A

    1999-08-01

    Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear.

  20. The kinetics of removal of heat-induced excess nuclear protein

    International Nuclear Information System (INIS)

    Roti, J.L.R.; Uygur, N.; Higashikubo, R.

    1984-01-01

    To investigate the role of protein content, temperature and heating time in the removal of heat-induced excess protein associated with the isolated nucleus, the kinetics of protein removal was monitored for 6 to 8 hours following exposure to 7 hyperthermic protocols. Four of these (47 0 C-7.5 min., 46 0 C-15 min., 45 0 C-30 min., and 44 0 C-60 min.) resulted in a nuclear protein content approximately twice that of nuclei from unheated cells (2.05 +- .14) following heat exposure. Three protocols (45 0 C-15 min., 44 0 C-30 min. and 43 0 C-60 min.) resulted in a nuclear protein content approximately 1.6 times normal (1.63 +- .12). If nuclear protein content were the only determinant in the recovery rate, then the same half time for nuclear protein removal would be expected within each group of protocols. Rate constants for nuclear protein removal were obtained by regression analysis. The half-time for nuclear protein removal increased with decreasing temperature and increasing heating time for the same nuclear protein content. This result suggests that the heating time and temperature are more of a determinant in the removal kinetics than protein content alone. Extended kinetics of recovery (to 36 hours) showed incomplete recovery and a secondary increase in protein associated with the isolated nucleus. These results were due to cell-cycle rearrangement (G/sub 2/ block) and unbalanced growth

  1. Communication of 29 April 1996 received from the permanent mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-06-07

    The Director General of the International Atomic Energy Agency has received a note verbale of 29 April 1996 from the Permanent Mission of the Russian Federation providing information on the export policies and practices of the Government of the Russian Federation with respect to nuclear transfers. In light of the request expressed in the note verbale, the text of the note verbale and its attachment is being circulated.

  2. Communication of 29 April 1996 received from the permanent mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General of the International Atomic Energy Agency has received a note verbale of 29 April 1996 from the Permanent Mission of the Russian Federation providing information on the export policies and practices of the Government of the Russian Federation with respect to nuclear transfers. In light of the request expressed in the note verbale, the text of the note verbale and its attachment is being circulated

  3. Jaw1/LRMP has a role in maintaining nuclear shape via interaction with SUN proteins.

    Science.gov (United States)

    Kozono, Takuma; Tadahira, Kazuko; Okumura, Wataru; Itai, Nao; Tamura-Nakano, Miwa; Dohi, Taeko; Tonozuka, Takashi; Nishikawa, Atsushi

    2018-06-06

    Jaw1/LRMP is characterized as a type II integral membrane protein that is localized to endoplasmic reticulum (ER), however, its physiological functions have been poorly understood. An alignment of amino acid sequence of Jaw1 with KASH proteins, outer nuclear membrane proteins, revealed that Jaw1 has a partial homology to the KASH domain. Here, we show that the function of Jaw1 is to maintain nuclear shape in mouse melanoma cell line. The siRNA-mediated knockdown of Jaw1 caused a severe defect in nuclear shape, and the defect was rescued by ectopic expression of siRNA-resistant Jaw1. Since co-immunoprecipitation assay indicates that Jaw1 interacts with SUN proteins that are inner nuclear proteins and microtubules, this study suggests that Jaw1 has a role in maintaining nuclear shape via interactions with SUN proteins and microtubules.

  4. Act of 9 Februray 1981 on the conditions for the export of nuclear material and equipment and of nuclear technological data

    International Nuclear Information System (INIS)

    1981-01-01

    The purpose of this Act is to implement international agreements on the non-proliferation of nuclear weapons and in particular, to prevent the transfer of materials, equipment and technological data likely to be used for non-peaceful purposes. Therefore each transfer of this type is subject to prior authorisation by the Minister responsible for energy, after consultation with an advisory committee made up of representatives of the Ministries concerned (NEA) [fr

  5. Interaction between a plasma membrane-localized ankyrin-repeat protein ITN1 and a nuclear protein RTV1

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Hikaru [Department of Bioproduction, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri-shi, Hokkaido 093-2422 (Japan); Sakata, Keiko; Kusumi, Kensuke [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Kojima, Mikiko; Sakakibara, Hitoshi [RIKEN Plant Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 (Japan); Iba, Koh, E-mail: koibascb@kyushu-u.org [Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer ITN1, a plasma membrane ankyrin protein, interacts with a nuclear DNA-binding protein RTV1. Black-Right-Pointing-Pointer The nuclear transport of RTV1 is partially inhibited by interaction with ITN1. Black-Right-Pointing-Pointer RTV1 can promote the nuclear localization of ITN1. Black-Right-Pointing-Pointer Both overexpression of RTV1 and the lack of ITN1 increase salicylic acids sensitivity in plants. -- Abstract: The increased tolerance to NaCl 1 (ITN1) protein is a plasma membrane (PM)-localized protein involved in responses to NaCl stress in Arabidopsis. The predicted structure of ITN1 is composed of multiple transmembrane regions and an ankyrin-repeat domain that is known to mediate protein-protein interactions. To elucidate the molecular functions of ITN1, we searched for interacting partners using a yeast two-hybrid assay, and a nuclear-localized DNA-binding protein, RTV1, was identified as a candidate. Bimolecular fluorescence complementation analysis revealed that RTV1 interacted with ITN1 at the PM and nuclei in vivo. RTV1 tagged with red fluorescent protein localized to nuclei and ITN1 tagged with green fluorescent protein localized to PM; however, both proteins localized to both nuclei and the PM when co-expressed. These findings suggest that RTV1 and ITN1 regulate the subcellular localization of each other.

  6. Export policy and non-proliferation

    International Nuclear Information System (INIS)

    Fischer, D.A.V.

    1978-01-01

    Developing countries with a nuclear programme are about a dozen according to information obtained by IAEA. They are a group hostile to any restriction imposed on nuclear technology export and consider that such restriction is contrary to the global concept of North/South co-operation which provides for transfer of advanced technology. In particular, they object to the fact that nuclear weapon states make use of Article 4 of the NPT. Industrialised countries are required to keep a balance between a regular and stable supply system and the assurance that exported nuclear installations and materials are placed under international control according to the IAEA Safeguards. (NEA) [fr

  7. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.

    Science.gov (United States)

    Milbradt, Jens; Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Sticht, Heinrich; Britt, William J; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

    2018-01-13

    The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

  8. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97

    Directory of Open Access Journals (Sweden)

    Jens Milbradt

    2018-01-01

    Full Text Available The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

  9. Export of radiopharmaceuticals and establishment of export base of cyclotron

    International Nuclear Information System (INIS)

    Jung, Kyungil; Kim, Youngsik

    2006-01-01

    Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

  10. Nuclear substructure reorganization during late stageerythropoiesis is selective and does not involve caspase cleavage ofmajor nuclear substructural proteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, Sharon Wald; Lo, Annie J.; Short, Sarah A.; Koury, MarkJ.; Mohandas, Narla; Chasis, Joel Anne

    2005-04-06

    Enucleation, a rare feature of mammalian differentiation, occurs in three cell types: erythroblasts, lens epithelium and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing BFU-E differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA, and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery.

  11. Resolution Improvement in Multidimensional Nuclear Magnetic Resonance Spectroscopy of Proteins

    International Nuclear Information System (INIS)

    Duma, L.

    2004-01-01

    The work presented in this thesis is concerned with both liquid-state and solid-state nuclear magnetic resonance (NMR) spectroscopy. Most of this work is devoted to the investigation by solid-state NMR of C 13 -enriched compounds with the principal aim of presenting techniques devised for further improving the spectral resolution in multidimensional NMR of microcrystalline proteins. In fully C 13 -labelled compounds, the J-coupling induces a broadening of the carbon lineshapes. We show that spin-state-selective technique called IPAP can be successfully combined with standard polarisation transfer schemes in order to remove the J-broadening in multidimensional solid-state NMR correlation experiments of fully C 13 -enriched proteins. We present subsequently two techniques tailored for liquid-state NMR spectroscopy. The carbon directly detected techniques provide chemical shift information for all backbone hetero-nuclei. They are very attracting for the study of large bio-molecular systems or for the investigation of paramagnetic proteins. In the last part of this thesis, we study the spin-echo J-modulation for homonuclear two-spin 1/2 systems. Under magic-angle spinning, the theory of J-induced spin-echo modulation allows to derive a set of modulation regimes which give a spin-echo modulation exactly equal to the J-coupling. We show that the chemical-shift anisotropy and the dipolar interaction tend to stabilize the spin-echo J-modulation. The theoretical conclusions are supported by numerical simulations and experimental results obtained for three representative samples containing C 13 spin pairs. (author)

  12. Analysis of Developed Country's Export Contract and Contract Risk and Development of Sample Contract and Guide

    International Nuclear Information System (INIS)

    Lee, D. S.; Oh, K. B.; Chung, W. S.; Lee, K. S.; Yun, S. W.; Lee, J. H.; Lee, B. W.; Kim, H. J.; Yang, M. H.

    2008-10-01

    This paper aimed at developing legal support for the non nuclear power plant industry's export. This study aids establishing government policy and promoting export of non nuclear power plant industry. This paper treated analysis of contractual risk and caution before entering into contract. To promote continuing export result, governmental and legal aids and guide will be required continuously. This study showed risks related with export contract and explained export control acts and procedures

  13. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology; Comunicaciones recibidas de ciertos Estados Miembros relativas a las directrices para la exportacion de materiales, equipos y tecnologia nucleares

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-06-12

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology [Spanish] El Director General del Organismo Internacional de Energia Atomica ha recibido notas verbales de fecha 1 de diciembre de 2005 de los Representantes Permanentes ante el Organismo de Alemania, Argentina, Australia, Austria, Belarus, Belgica, Brasil, Bulgaria, Canada, China, Croacia, Eslovenia, Espana, Estados Unidos de America, Finlandia, Francia, Grecia, Hungria, Irlanda, Italia, Japon, Letonia, Lituania, Luxemburgo, Malta, Nueva Zelandia, Paises Bajos, Polonia, Portugal, Reino Unido de Gran Bretana e Irlanda del Norte, Republica Checa, Republica de Corea, Sudafrica, Suecia, Suiza, Turquia y Ucrania relativas a la exportacion de materiales, equipo y tecnologia nucleares.

  14. The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent.

    Science.gov (United States)

    Tsuji, Takahiro; Sheehy, Noreen; Gautier, Virginie W; Hayakawa, Hitoshi; Sawa, Hirofumi; Hall, William W

    2007-05-04

    HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection.

  15. The nuclear import of ribosomal proteins is regulated by mTOR

    Science.gov (United States)

    Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

    2014-01-01

    Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

  16. Case Law: - Canada: Criminal Court decision respecting attempted export of nuclear-related dual use items to Iran: Her Majesty the Queen vs Yadegari (2010); - Czech Republic: Supreme Administrative Court on the legal status of CEZ (2010)

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Case law 1: Canada - Criminal Court decision respecting attempted export of nuclear-related dual use items to Iran: Her Majesty the Queen vs Yadegari (2010). This case concerns a recent, successful prosecution that was undertaken before the Ontario Court of Justice relating to violations of export control legislation in Canada, nuclear regulatory legislation, customs law, criminal law, as well as Canadian law implementing UN Security Council resolutions concerning Iran. The convictions that have been registered in this case, notwithstanding the fact that the decision is currently under appeal,2 demonstrate the importance of a functioning export control regime and effective counter-proliferation strategy. The case represents the first conviction for a regulatory offense under the Nuclear Safety and Control Act,3 in force since 2000, and Mr. Yadegari is the first Canadian to be convicted under the United Nations Act, Canada's legislation by which it implements UN resolutions. Case law 2: Czech Republic - Supreme Administrative Court on the legal status of CEZ (2010). The Supreme Administrative Court in its decision of 6 October 20098 ruled on whether CEZ, a.s., which is the operator of nuclear installations at the Temelin and Dukovany sites in the Czech Republic, is governed by the Act on Free Access to Information. The court stated that the rules laid down in the Act on Free Access to Information, also apply to CEZ which is considered as a 'public institution'. The following reasons led the court to this interpretation: first, CEZ was established by decision of the state in the course of the privatisation process. Secondly, the company is effectively controlled by the state, which is still its majority owner and the profits of the company also compose a portion of state budget revenues. Finally, there is a public interest served in the function of the company

  17. UNcleProt (Universal Nuclear Protein database of barley): The first nuclear protein database that distinguishes proteins from different phases of the cell cycle

    Czech Academy of Sciences Publication Activity Database

    Blavet, Nicolas; Uřinovská, J.; Jeřábková, Hana; Chamrád, I.; Vrána, Jan; Lenobel, R.; Beinhauer, D.; Šebela, M.; Doležel, Jaroslav; Petrovská, Beáta

    2017-01-01

    Roč. 8, č. 1 (2017), s. 70-80 ISSN 1949-1034 R&D Projects: GA ČR(CZ) GA14-28443S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : cicer-arietinum l. * rice oryza-sativa * chromatin-associated protein s * proteomic analysis * mitotic chromosomes * dehydration * localization * chickpea * network * phosphoproteome * barley * cell cycle * database * flow-cytometry * localization * mass spectrometry * nuclear proteome * nucleus Subject RIV: CE - Biochemistry OBOR OECD: Cell biology Impact factor: 2.387, year: 2016

  18. The SUN protein Mps3 is required for spindle pole body insertion into the nuclear membrane and nuclear envelope homeostasis.

    Directory of Open Access Journals (Sweden)

    Jennifer M Friederichs

    2011-11-01

    Full Text Available The budding yeast spindle pole body (SPB is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition.

  19. Identification of a nuclear localization signal in the retinitis pigmentosa-mutated RP26 protein, ceramide kinase-like protein

    International Nuclear Information System (INIS)

    Inagaki, Yuichi; Mitsutake, Susumu; Igarashi, Yasuyuki

    2006-01-01

    Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by degeneration of the retina. A mutation in a new ceramide kinase (CERK) homologous gene, named CERK-like protein (CERKL), was found to cause autosomal recessive retinitis pigmentosa (RP26). Here, we show a point mutation of one of two putative nuclear localization signal (NLS) sequences inhibited the nuclear localization of the protein. Furthermore, the tetra-GFP-tagged NLS, which cannot passively enter the nucleus, was observed not only in the nucleus but also in the nucleolus. Our results provide First evidence of the active nuclear import of CERKL and suggest that the identified NLS might be responsible for nucleolar retention of the protein. As recent studies have shown other RP-related proteins are localized in the nucleus or the nucleolus, our identification of NLS in CERKL suggests that CERKL likely plays important roles for retinal functions in the nucleus and the nucleolus

  20. The nuclear IκB family of proteins controls gene regulation and immune homeostasis.

    Science.gov (United States)

    MaruYama, Takashi

    2015-10-01

    The inhibitory IκB family of proteins is subdivided into two groups based on protein localization in the cytoplasm or in the nucleus. These proteins interact with NF-κB, a major transcription factor regulating the expression of many inflammatory cytokines, by modulating its transcriptional activity. However, nuclear IκB family proteins not only interact with NF-κB to change its transcriptional activity, but they also bind to chromatin and control gene expression. This review provides an overview of nuclear IκB family proteins and their role in immune homeostasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Understanding renal nuclear protein accumulation: an in vitro approach to explain an in vivo phenomenon.

    Science.gov (United States)

    Luks, Lisanne; Maier, Marcia Y; Sacchi, Silvia; Pollegioni, Loredano; Dietrich, Daniel R

    2017-11-01

    Proper subcellular trafficking is essential to prevent protein mislocalization and aggregation. Transport of the peroxisomal enzyme D-amino acid oxidase (DAAO) appears dysregulated by specific pharmaceuticals, e.g., the anti-overactive bladder drug propiverine or a norepinephrine/serotonin reuptake inhibitor (NSRI), resulting in massive cytosolic and nuclear accumulations in rat kidney. To assess the underlying molecular mechanism of the latter, we aimed to characterize the nature of peroxisomal and cyto-nuclear shuttling of human and rat DAAO overexpressed in three cell lines using confocal microscopy. Indeed, interference with peroxisomal transport via deletion of the PTS1 signal or PEX5 knockdown resulted in induced nuclear DAAO localization. Having demonstrated the absence of active nuclear import and employing variably sized mCherry- and/or EYFP-fusion proteins of DAAO and catalase, we showed that peroxisomal proteins ≤134 kDa can passively diffuse into mammalian cell nuclei-thereby contradicting the often-cited 40 kDa diffusion limit. Moreover, their inherent nuclear presence and nuclear accumulation subsequent to proteasome inhibition or abrogated peroxisomal transport suggests that nuclear localization is a characteristic in the lifecycle of peroxisomal proteins. Based on this molecular trafficking analysis, we suggest that pharmaceuticals like propiverine or an NSRI may interfere with peroxisomal protein targeting and import, consequently resulting in massive nuclear protein accumulation in vivo.

  2. Exports and Job Training

    OpenAIRE

    Bastos, Paulo; Silva, Joana; Proenca, Rafael

    2016-01-01

    This paper examines whether export participation matters for job training. The paper draws on longitudinal worker-firm data for Brazilian manufacturing, linked with detailed records on training activity from the main provider. The analysis uses industry-specific exchange rate movements to generate exogenous variation in export status at the firm-level. The findings indicate that export par...

  3. Renewable energy export network

    International Nuclear Information System (INIS)

    Anon

    2000-01-01

    A Renewable Energy Exporters Network (REEN) has recently been established, following a meeting of renewable energy exporters and government agencies on 30 October 2000. REEN will assist the Australian renewable energy industry to take advantage of the opportunities offered by the burgeoning global market for renewable energy goods and services. Recent estimates of the significant potential global growth is renewable energy demand have reinforced the industry and Government's view that, in the medium to long-term, growth in the Australian renewable energy industry will largely depend on capturing export market share. Expanding the export market was identified as a crucial component in the Renewable Energy Action Agenda, developed jointly by industry and Government and released in June 2000. It was estimated that, for the industry to achieve its vision of sales of $4 billion per year by 2010, exports would need to comprise approximately 50% of the forecast growth in sales. As such, the need for a specific export strategy for the Australian renewable energy industry was recognised in the Action Agenda, and the establishment of the REEN is one of the first initiatives undertaken as part of the Renewable Energy Export Strategy. The REEN comprises approximately 50 export-ready renewable energy companies, the Department of Industry, Science and Resources, Austrade, and Stage Government agencies such as NSW's Sustainable Energy Development Authority. The Export Network will operate electronically, with face-to-face meetings held as appropriate. The Department of Industry, Science and Resources will facilitate the Export Network and has published a website at www.isr.gov.au/industry/reen. The site includes: a members directory; a discussion forum; information on opportunities to showcase Australian renewable; energy products and services; and Iinks to sites containing information that may be useful to renewable energy exporters. Other actions that are being undertaken as

  4. Interactions of rat repetitive sequence MspI8 with nuclear matrix proteins during spermatogenesis

    International Nuclear Information System (INIS)

    Rogolinski, J.; Widlak, P.; Rzeszowska-Wolny, J.

    1996-01-01

    Using the Southwestern blot analysis we have studied the interactions between rat repetitive sequence MspI8 and the nuclear matrix proteins of rats testis cells. Starting from 2 weeks the young to adult animal showed differences in type of testis nuclear matrix proteins recognizing the MspI8 sequence. The same sets of nuclear matrix proteins were detected in some enriched in spermatocytes and spermatids and obtained after fractionation of cells of adult animal by the velocity sedimentation technique. (author). 21 refs, 5 figs

  5. An early function of the adenoviral E1B 55 kDa protein is required for the nuclear relocalization of the cellular p53 protein in adenovirus-infected normal human cells

    International Nuclear Information System (INIS)

    Cardoso, F.M.; Kato, Sayuri E.M.; Huang Wenying; Flint, S. Jane; Gonzalez, Ramon A.

    2008-01-01

    It is well established that the human subgroup C adenovirus type 5 (Ad5) E1B 55 kDa protein can regulate the activity and concentration of the cellular tumor suppressor, p53. However, the contribution(s) of these functions of the E1B protein to viral reproduction remains unclear. To investigate this issue, we examined properties of p53 in normal human cells infected by E1B mutant viruses that display defective entry into the late phase or viral late mRNA export. The steady-state concentrations of p53 were significantly higher in cells infected by the E1B 55 kDa null mutant Hr6 or three mutants carrying small insertions in the E1B 55 kDa protein coding sequence than in Ad5-infected cells. Nevertheless, none of the mutants induced apoptosis in infected cells. Rather, the localization of p53 to E1B containing nuclear sites observed during infection by Ad5 was prevented by mutations that impair interaction of the E1B protein with p53 and/or with the E4 Orf6 protein. These results indicate that the E1B protein fulfills an early function that correlates efficient entry into the late phase with the localization of E1B and p53 in the nucleus of Ad5-infected normal human cells

  6. ANP32B is a nuclear target of henipavirus M proteins.

    Directory of Open Access Journals (Sweden)

    Anja Bauer

    Full Text Available Membrane envelopment and budding of negative strand RNA viruses (NSVs is mainly driven by viral matrix proteins (M. In addition, several M proteins are also known to be involved in host cell manipulation. Knowledge about the cellular targets and detailed molecular mechanisms, however, is poor for many M proteins. For instance, Nipah Virus (NiV M protein trafficking through the nucleus is essential for virus release, but nuclear targets of NiV M remain unknown. To identify cellular interactors of henipavirus M proteins, tagged Hendra Virus (HeV M proteins were expressed and M-containing protein complexes were isolated and analysed. Presence of acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B in the complex suggested that this protein represents a direct or indirect interactor of the viral matrix protein. Over-expression of ANP32B led to specific nuclear accumulation of HeV M, providing a functional link between ANP32B and M protein. ANP32B-dependent nuclear accumulation was observed after plasmid-driven expression of HeV and NiV matrix proteins and also in NiV infected cells. The latter indicated that an interaction of henipavirus M protein with ANP32B also occurs in the context of virus replication. From these data we conclude that ANP32B is a nuclear target of henipavirus M that may contribute to virus replication. Potential effects of ANP32B on HeV nuclear shuttling and host cell manipulation by HeV M affecting ANP32B functions in host cell survival and gene expression regulation are discussed.

  7. mRNA export in the apicomplexan parasite Toxoplasma gondii: emerging divergent components of a crucial pathway.

    Science.gov (United States)

    Ávila, Andréa Rodrigues; Cabezas-Cruz, Alexjandro; Gissot, Mathieu

    2018-01-25

    Control of gene expression is crucial for parasite survival and is the result of a series of processes that are regulated to permit fine-tuning of gene expression in response to biological changes during the life-cycle of apicomplexan parasites. Control of mRNA nuclear export is a key process in eukaryotic cells but is poorly understood in apicomplexan parasites. Here, we review recent knowledge regarding this process with an emphasis on T. gondii. We describe the presence of divergent orthologs and discuss structural and functional differences in export factors between apicomplexans and other eukaryotic lineages. Undoubtedly, the use of the CRISPR/Cas9 system in high throughput screenings associated with the discovery of mRNA nuclear export complexes by proteomic analysis will contribute to identify these divergent factors. Ligand-based or structure-based strategies may be applied to investigate the potential use of these proteins as targets for new antiprotozoal agents.

  8. Exporting and Productivity

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    2017-01-01

    different policy stance than typical in Africa. This is especially so in promoting export-oriented industry. If learning by exporting is a key driver of progress, then a fundamental reason for Africa's lack of transformation is likely to be the low policy priority given to export promotion in the past....... To enlarge the body of empirical evidence, we use an extensive 2005–2012 firm-level panel data set from Vietnam and separate out productivity effects of exporting due to self-selection. This allows us to conclude that firms actually learn by exporting. We also examine how this learning takes place. Our...... findings suggest that productivity gains are associated with moving to larger scale for foreign-owned firms with little evidence of subsequent learning on export markets. We find strong evidence to suggest that private domestic firms learn and accumulate knowledge from export markets with learning...

  9. Act of 18 December 1987 relating to the control of the export of strategic goods, services and technology

    International Nuclear Information System (INIS)

    1987-01-01

    This Act controls the export of nuclear material and equipment and sensitive nuclear technology and services. In particular, it provides for strict controls and verification of certain exports. (NEA) [fr

  10. Control of nuclear β-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function.

    Science.gov (United States)

    Vélez-Aguilera, Griselda; de Dios Gómez-López, Juan; Jiménez-Gutiérrez, Guadalupe E; Vásquez-Limeta, Alejandra; Laredo-Cisneros, Marco S; Gómez, Pablo; Winder, Steve J; Cisneros, Bulmaro

    2018-02-01

    β-Dystroglycan (β-DG) is a plasma membrane protein that has ability to target to the nuclear envelope (NE) to maintain nuclear architecture. Nevertheless, mechanisms controlling β-DG nuclear localization and the physiological consequences of a failure of trafficking are largely unknown. We show that β-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its transmembrane domain, by CRM1. Remarkably, NES mutations forced β-DG nuclear accumulation resulting in mislocalization and decreased levels of emerin and lamin B1 and disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and β-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are critically involved. In addition to nuclear export, the lifespan of nuclear β-DG is restricted by its nuclear proteasomal degradation. Collectively our data show that control of nuclear β-DG content by the combination of CRM1 nuclear export and nuclear proteasome pathways is physiologically relevant to preserve proper NE structure and activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The proteins of intra-nuclear bodies: a data-driven analysis of sequence, interaction and expression

    Directory of Open Access Journals (Sweden)

    Bodén Mikael

    2010-04-01

    Full Text Available Abstract Background Cajal bodies, nucleoli, PML nuclear bodies, and nuclear speckles are morpohologically distinct intra-nuclear structures that dynamically respond to cellular cues. Such nuclear bodies are hypothesized to play important regulatory roles, e.g. by sequestering and releasing transcription factors in a timely manner. While the nucleolus and nuclear speckles have received more attention experimentally, the PML nuclear body and the Cajal body are still incompletely characterized in terms of their roles and protein complement. Results By collating recent experimentally verified data, we find that almost 1000 proteins in the mouse nuclear proteome are known to associate with one or more of the nuclear bodies. Their gene ontology terms highlight their regulatory roles: splicing is confirmed to be a core activity of speckles and PML nuclear bodies house a range of proteins involved in DNA repair. We train support-vector machines to show that nuclear proteins contain discriminative sequence features that can be used to identify their intra-nuclear body associations. Prediction accuracy is highest for nucleoli and nuclear speckles. The trained models are also used to estimate the full protein complement of each nuclear body. Protein interactions are found primarily to link proteins in the nuclear speckles with proteins from other compartments. Cell cycle expression data provide support for increased activity in nucleoli, nuclear speckles and PML nuclear bodies especially during S and G2 phases. Conclusions The large-scale analysis of the mouse nuclear proteome sheds light on the functional organization of physically embodied intra-nuclear compartments. We observe partial support for the hypothesis that the physical organization of the nucleus mirrors functional modularity. However, we are unable to unambiguously identify proteins' intra-nuclear destination, suggesting that critical drivers behind of intra-nuclear translocation are yet to

  12. Fanconi Anemia Proteins FANCA, FANCC, and FANCG/XRCC9 Interact in a Functional Nuclear Complex

    OpenAIRE

    Garcia-Higuera, Irene; Kuang, Yanan; Näf, Dieter; Wasik, Jennifer; D’Andrea, Alan D.

    1999-01-01

    Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least eight complementation groups (A to H). Three FA genes, corresponding to complementation groups A, C, and G, have been cloned, but their cellular function remains unknown. We have previously demonstrated that the FANCA and FANCC proteins interact and form a nuclear complex in normal cells, suggesting that the proteins cooperate in a nuclear function. In this report, we demonstrate that the recently clone...

  13. Export and import. Conformity with regulations

    International Nuclear Information System (INIS)

    Shapar, M.

    1976-01-01

    Since the division of the former US Atomic Energy Commission's tasks, the regulation and control of import and export of nuclear materials and equipment has become the responsability of the Nuclear Regulatory Commission (NRC). The import and export of nuclear fuels, equipment and reactors are therefore subject to prior licensing by the Commission. This requirement aims to guarantee that such activities will not create serious hazards for defense and national safety, and that the exported products will not be diverted from their peaceful uses. The relevant applicable legal provisions are based on the Atomic Energy Act of 1954 and on the detailed regulations issued by the Commission. Under the pressure of public opinion, there is a current tendency to restrict these activities because of the hazards they present, in particular during transport, until the Commission has completed all the necessary studies. (NEA) [fr

  14. Should Australia mine and export uranium?

    International Nuclear Information System (INIS)

    Cobb, M.; Broadbent, Steve.

    1989-01-01

    In this chapter, the case for and against the mining and export of Australian uranium is discussed. For those in favour of uranium export, the nuclear energy, a source of energy which could bring a much needed boost to Australian export and employment, is being stifled by specious 'scare tactics' about the danger and misuse of uranium. It is also shown that uranium is the only feasible energy source, being cheaper, safer and cleaner when compared with other energy sources. Meanwhile, the opponents of nuclear energy, argue that uranium mining is environmentally destructive, is a danger to workers and residents health, it is bad for economy and it provides raw materials for nuclear weapons. 2 tabs

  15. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

    NARCIS (Netherlands)

    Ketterer, Philip; Ananth, Adithya N; Laman Trip, Diederik S; Mishra, Ankur; Bertosin, Eva; Ganji, Mahipal; van der Torre, Jaco; Onck, Patrick; Dietz, Hendrik; Dekker, Cees

    2018-01-01

    The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize

  16. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

    NARCIS (Netherlands)

    Ketterer, Philip; Ananth, A.N.; Laman Trip, J.D.S.; Mishra, Ankur; Bertosin, Eva; Ganji, M.; van der Torre, J.; Onck, Patrick; Dietz, Hendrik; Dekker, C.

    2018-01-01

    The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize

  17. Characterization of a baculovirus nuclear localization signal domain in the late expression factor 3 protein

    International Nuclear Information System (INIS)

    Au, Victoria; Yu Mei; Carstens, Eric B.

    2009-01-01

    The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) single-stranded DNA binding protein LEF-3 is a multi-functional protein that is required to transport the helicase protein P143 into the nucleus of infected cells where they function to replicate viral DNA. The N-terminal 56 amino acid region of LEF-3 is required for nuclear transport. In this report, we analyzed the effect of site-specific mutagenesis of LEF-3 on its intracellular distribution. Fluorescence microscopy of expression plasmid-transfected cells demonstrated that the residues 28 to 32 formed the core nuclear localization signal, but other adjacent positively-charged residues augmented these sequences. Comparison with other group I Alphabaculoviruses suggested that this core region functionally duplicated residues including 18 and 19. This was demonstrated by the loss of nuclear localization when the equivalent residues (18 to 20) in Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) LEF-3 were mutated. The AcMNPV LEF-3 nuclear localization domain was also shown to drive nuclear transport in mammalian cells indicating that the protein nuclear import systems in insect and mammalian cells are conserved. We also demonstrated by mutagenesis that two conserved cysteine residues located at 82 and 106 were not essential for nuclear localization or for interaction with P143. However, by using a modified construct of P143 that localized on its own to the nucleus, we demonstrated that a functional nuclear localization domain on LEF-3 was required for interaction between LEF-3 and P143

  18. Isolation of nuclear proteins from flax (Linum usitatissimum L. seed coats for gene expression regulation studies

    Directory of Open Access Journals (Sweden)

    Renouard Sullivan

    2012-01-01

    Full Text Available Abstract Background While seed biology is well characterized and numerous studies have focused on this subject over the past years, the regulation of seed coat development and metabolism is for the most part still non-elucidated. It is well known that the seed coat has an essential role in seed development and its features are associated with important agronomical traits. It also constitutes a rich source of valuable compounds such as pharmaceuticals. Most of the cell genetic material is contained in the nucleus; therefore nuclear proteins constitute a major actor for gene expression regulation. Isolation of nuclear proteins responsible for specific seed coat expression is an important prerequisite for understanding seed coat metabolism and development. The extraction of nuclear proteins may be problematic due to the presence of specific components that can interfere with the extraction process. The seed coat is a rich source of mucilage and phenolics, which are good examples of these hindering compounds. Findings In the present study, we propose an optimized nuclear protein extraction protocol able to provide nuclear proteins from flax seed coat without contaminants and sufficient yield and quality for their use in transcriptional gene expression regulation by gel shift experiments. Conclusions Routinely, around 250 μg of nuclear proteins per gram of fresh weight were extracted from immature flax seed coats. The isolation protocol described hereafter may serve as an effective tool for gene expression regulation and seed coat-focused proteomics studies.

  19. Dual localized mitochondrial and nuclear proteins as gene expression regulators in plants?

    Directory of Open Access Journals (Sweden)

    Philippe eGiegé

    2012-09-01

    Full Text Available Mitochondria heavily depend on the coordinated expression of both mitochondrial and nuclear genomes because some of their most significant activities are held by multi-subunit complexes composed of both mitochondrial and nuclear encoded proteins. Thus, precise communication and signaling pathways are believed to exist between the two compartments. Proteins dual localized to both mitochondria and the nucleus make excellent candidates for a potential involvement in the envisaged communication. Here, we review the identified instances of dual localized nucleo-mitochondrial proteins with an emphasis on plant proteins and discuss their functions, which are seemingly mostly related to gene expression regulation. We discuss whether dual localization could be achieved by dual targeting and / or by re-localization and try to apprehend the signals required for the respective processes. Finally, we propose that in some instances, dual localized mitochondrial and nuclear proteins might act as retrograde signaling molecules for mitochondrial biogenesis.

  20. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

    International Nuclear Information System (INIS)

    Mao, Grace; Brody, James P.

    2007-01-01

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s -1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase