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Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor α-stimulated nuclear factor κB activation

Title
Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor α-stimulated nuclear factor κB activation
Authors
Park K.-J.Choi S.-H.Lee S.Y.Hwang S.B.Lai M.M.C.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopusscopus
Issue Date
2002
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
Journal of Biological Chemistry vol. 277, no. 15, pp. 13122 - 13128
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The hepatitis C virus nonstructural protein 5A (NS5A) is a multifunctional phosphoprotein that leads to pleiotropic responses, in part by regulating cell growth and cellular signaling pathways. Here we show that overexpression of NS5A inhibits tumor necrosis factor (TNF)-α-induced nuclear factor κB (NF-κB) activation in HEK293 cells, as determined by luciferase reporter gene expression and by electrophoretic mobility shift assay. When overexpressed, NS5A cannot inhibit the recruitment of TNF receptor-associated factor 2 (TRAF2) and IκB kinase (IKK)β into the TNF receptor 1-TNF receptor-associated death domain complex. In contrast, NS5A is a part of the TNF receptor 1 signaling complex. NF-κB activation by TNF receptor-associated death domain and TRAF2 was inhibited by NS5A, whereas MEKK1 and IKKβ-dependent NF-κB activation was not affected, suggesting that NS5A may inhibit NF-κB activation signaled by TRAF2. Coimmunoprecipitation and colocalization of NS5A and TRAF2 expressed in vivo provide compelling evidence that NS5A directly interacts with TRAF2. This interaction was mapped to the middle one-third (amino acids 148-301) of NS5A and the TRAF domain of TRAF2. Our findings suggest a possible molecular mechanism that could explain the ability of NS5A to negatively regulate TNF-α-induced NF-κB activation.
DOI
10.1074/jbc.M111599200
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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