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Hepatitis C virus NS5A protein modulates c-Jun N-terminal kinase through interaction with tumor necrosis factor receptor-associated factor 2
- Title
- Hepatitis C virus NS5A protein modulates c-Jun N-terminal kinase through interaction with tumor necrosis factor receptor-associated factor 2
- Authors
- Park K.-J.; Choi S.-H.; Choi D.-H.; Park J.-M.; Yie S.W.; Lee S.Y.; Hwang S.B.
- Ewha Authors
- 이수영
- SCOPUS Author ID
- 이수영
- Issue Date
- 2003
- Journal Title
- Journal of Biological Chemistry
- ISSN
- 0021-9258
- Citation
- Journal of Biological Chemistry vol. 278, no. 33, pp. 30711 - 30718
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a phosphoprotein possessing various functions. We have previously reported that the HCV NS5A protein interacts with tumor necrosis factor (TNF) receptor-associated factor (TRAF) domain of TRAF2 (Park, K.-J., Choi, S.-H., Lee, S. Y., Hwang, S. B., and Lai, M. M. C. (2002) J. Biol. Chem. 277, 13122-13128). Both TNF-α- and TRAF2-mediated nuclear factor-κB (NF-κB) activations were inhibited by NS5A-TRAF2 interaction. Because TRAF2 is required for the activation of both NF-κB and c-Jun N-terminal kinase (JNK), we investigated HCV NS5A protein for its potential capacity to modulate TRAF2-mediated JNK activity. Using in vitro kinase assay, we have found that NS5A protein synergistically activated both TNF-α- and TRAF2-medidated JNK in human embryonic kidney 293T cells. Furthermore, synergism of NS5A-mediated JNK activation was inhibited by dominant-negative form of MEK kinase 1. Our in vivo binding data show that NS5A does not inhibit interaction between TNF receptor-associated death domain and TRAF2 protein, indicating that NS5A and TRAF2 may form a ternary complex with TNF receptor-associated death domain. These results indicate that HCV NS5A protein modulates TNF signaling of the host cells and may play a role in HCV pathogenesis.
- DOI
- 10.1074/jbc.M209623200
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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