SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus
Identifieur interne : 000C28 ( Main/Exploration ); précédent : 000C27; suivant : 000C29SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus
Auteurs : Kulbhushan Sharma [Inde] ; Sara Kerström [Suède] ; Anuj Kumar Sharma [Inde] ; Vincent T. K. Chow [Singapour] ; Shumein Teow [Canada] ; Bernard Abrenica [Canada] ; Stephanie A. Booth [Canada] ; Timothy F. Booth [Canada] ; Ali Mirazimi [Suède] ; Sunil K. Lal [Inde]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood.
In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity.
Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.
Url:
DOI: 10.1371/journal.pone.0019436
PubMed: 21637748
PubMed Central: 3103500
Affiliations:
- Canada, Inde, Singapour, Suède
- Manitoba
- Winnipeg
- Université du Manitoba, Université nationale de Singapour
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000699
- to stream Pmc, to step Curation: 000699
- to stream Pmc, to step Checkpoint: 000539
- to stream Ncbi, to step Merge: 000223
- to stream Ncbi, to step Curation: 000223
- to stream Ncbi, to step Checkpoint: 000223
- to stream Main, to step Merge: 000C30
- to stream Main, to step Curation: 000C28
Le document en format XML
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K." last="Chow">Vincent T. K. Chow</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>The YLL School of Medicine, National University of Singapore, Kent Ridge, Singapore, Singapore</addr-line></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>The YLL School of Medicine, National University of Singapore, Kent Ridge, Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Teow, Shumein" sort="Teow, Shumein" uniqKey="Teow S" first="Shumein" last="Teow">Shumein Teow</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Abrenica, Bernard" sort="Abrenica, Bernard" uniqKey="Abrenica B" first="Bernard" last="Abrenica">Bernard Abrenica</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Booth, Stephanie A" sort="Booth, Stephanie A" uniqKey="Booth S" first="Stephanie A." last="Booth">Stephanie A. Booth</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff6"><addr-line>The Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Booth, Timothy F" sort="Booth, Timothy F" uniqKey="Booth T" first="Timothy F." last="Booth">Timothy F. Booth</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff6"><addr-line>The Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The Department of Medical Microbiology, University of Manitoba, Basic Medical Sciences Building, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Mirazimi, Ali" sort="Mirazimi, Ali" uniqKey="Mirazimi A" first="Ali" last="Mirazimi">Ali Mirazimi</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Swedish Institute for Communicable Disease Control, Solna, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Swedish Institute for Communicable Disease Control, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lal, Sunil K" sort="Lal, Sunil K" uniqKey="Lal S" first="Sunil K." last="Lal">Sunil K. Lal</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India</addr-line></nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>9b is an accessory protein of the SARS-CoV. It is a small protein of 98 amino acids and its structure has been solved recently. 9b is known to localize in the extra-nuclear region and has been postulated to possess a nuclear export signal (NES), however the role of NES in 9b functioning is not well understood.</p></sec><sec><title>Principal Findings/Methodology</title><p>In this report, we demonstrate that 9b in the absence of any nuclear localization signal (NLS) enters the nucleus by passive transport. Using various cell cycle inhibitors, we have shown that the nuclear entry of 9b is independent of the cell cycle. Further, we found that 9b interacts with the cellular protein Crm1 and gets exported out of the nucleus using an active NES. We have also revealed that this NES activity influences the half-life of 9b and affects host cell death. We found that an export signal deficient SARS-CoV 9b protein induces apoptosis in transiently transfected cells and showed elevated caspase-3 activity.</p></sec><sec><title>Conclusion/Significance</title><p>Here, we showed that nuclear shuttling of 9b and its interaction with Crm1 are essential for the proper degradation of 9b and blocking the nuclear export of this protein induces apoptosis. This phenomenon may be critical in providing a novel role to the 9b accessory protein of SARS-CoV.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Lee, N" uniqKey="Lee N">N Lee</name></author><author><name sortKey="Hui, D" uniqKey="Hui D">D Hui</name></author><author><name sortKey="Wu, A" uniqKey="Wu A">A Wu</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P Chan</name></author><author><name sortKey="Cameron, P" uniqKey="Cameron P">P Cameron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S Gunther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W Preiser</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S van der Werf</name></author><author><name sortKey="Brodt, Hr" uniqKey="Brodt H">HR 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Lin</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Inde</li><li>Singapour</li><li>Suède</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li><li>Université nationale de Singapour</li></orgName></list><tree><country name="Inde"><noRegion><name sortKey="Sharma, Kulbhushan" sort="Sharma, Kulbhushan" uniqKey="Sharma K" first="Kulbhushan" last="Sharma">Kulbhushan Sharma</name></noRegion><name sortKey="Lal, Sunil K" sort="Lal, Sunil K" uniqKey="Lal S" first="Sunil K." last="Lal">Sunil K. Lal</name><name sortKey="Sharma, Anuj Kumar" sort="Sharma, Anuj Kumar" uniqKey="Sharma A" first="Anuj Kumar" last="Sharma">Anuj Kumar Sharma</name></country><country name="Suède"><noRegion><name sortKey=" Kerstrom, Sara" sort=" Kerstrom, Sara" uniqKey=" Kerstrom S" first="Sara" last=" Kerström">Sara Kerström</name></noRegion><name sortKey="Mirazimi, Ali" sort="Mirazimi, Ali" uniqKey="Mirazimi A" first="Ali" last="Mirazimi">Ali Mirazimi</name></country><country name="Singapour"><noRegion><name sortKey="Chow, Vincent T K" sort="Chow, Vincent T K" uniqKey="Chow V" first="Vincent T. K." last="Chow">Vincent T. K. Chow</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Teow, Shumein" sort="Teow, Shumein" uniqKey="Teow S" first="Shumein" last="Teow">Shumein Teow</name></noRegion><name sortKey="Abrenica, Bernard" sort="Abrenica, Bernard" uniqKey="Abrenica B" first="Bernard" last="Abrenica">Bernard Abrenica</name><name sortKey="Booth, Stephanie A" sort="Booth, Stephanie A" uniqKey="Booth S" first="Stephanie A." last="Booth">Stephanie A. Booth</name><name sortKey="Booth, Stephanie A" sort="Booth, Stephanie A" uniqKey="Booth S" first="Stephanie A." last="Booth">Stephanie A. Booth</name><name sortKey="Booth, Timothy F" sort="Booth, Timothy F" uniqKey="Booth T" first="Timothy F." last="Booth">Timothy F. Booth</name><name sortKey="Booth, Timothy F" sort="Booth, Timothy F" uniqKey="Booth T" first="Timothy F." last="Booth">Timothy F. Booth</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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