| Langat flavivirus protease NS3 binds caspase-8 and induces apoptosis. | |
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MedLine Citation:
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PMID: 11991998 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The flavivirus NS3 protein plays an important role in the cleavage and processing of the viral polyprotein and in the synthesis of the viral RNA. NS3 recruits NS2B and NS5 proteins to form complexes possessing protease and replicase activities through protease and nucleoside triphosphatase/helicase domains. We have found that NS3 also induces apoptosis. Expression of the Langat (LGT) virus NS3 protein resulted in a cleavage of cellular DNA and reduced the viability of cells. Coexpression of NS3 with apoptotic inhibitors (CrmA and P35) and addition of caspase peptide substrates (Z-VAD-FMK and Z-IETD-FMK) to NS3-transfected cells blocked NS3-induced apoptosis. In cotransfection experiments, NS3 bound to caspase-8 and enhanced caspase-8-mediated apoptosis. NS3 and caspase-8 colocalized in the cytoplasm of transfected cells. Deletion analysis demonstrated that at least two regions of NS3 contribute to its apoptotic activities. The protease and helicase domains are each able to bind to caspase-8, while the protease domain alone induces apoptosis. The protease domain and tetrahelix region of the helicase domain are required for NS3 to augment caspase-8-mediated apoptosis. Thus, the LGT virus NS3 protein is a multifunctional protein that binds to caspase-8 and induces apoptosis. |
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Authors:
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Grigori G Prikhod'ko; Elena A Prikhod'ko; Alexander G Pletnev; Jeffrey I Cohen |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of virology Volume: 76 ISSN: 0022-538X ISO Abbreviation: J. Virol. Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-05-06 Completed Date: 2002-06-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 5701-10 Citation Subset: IM |
Affiliation:
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Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. PrikhodkoG@usa.redcross.org |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Binding Sites Caspase 8 Caspase 9 Caspases / genetics, metabolism* Cell Line, Transformed Cercopithecus aethiops Encephalitis Viruses, Tick-Borne / enzymology*, genetics Humans Mice RNA Helicases Recombinant Fusion Proteins / genetics, metabolism Serine Endopeptidases Tumor Cells, Cultured Vero Cells Viral Nonstructural Proteins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/NS3 protein, flavivirus; 0/Recombinant Fusion Proteins; 0/Viral Nonstructural Proteins; EC 2.7.7.-/RNA Helicases; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
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