Hepatitis C virus core protein potentiates TNF-alpha-induced NF-kappaB activation through TRAF2-IKKbeta-dependent pathway |
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Authors: | Chung Y M Park K J Choi S Y Hwang S B Lee S Y |
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Institution: | Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul, 120-750, Korea. |
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Abstract: | Previous work has implicated that the core protein of hepatitis C virus (HCV) may play a modulatory effect on NF-kappaB activation induced by TNF-alpha. However, it is unclear how HCV core protein modulates TNF-alpha-induced NK-kappaB activation. Here we show that overexpression of HCV core protein potentiates NF-kappaB activation induced by TNF-alpha. Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates NF-kappaB activation through TRAF2. Moreover, we demonstrate that HCV core protein potentiates TRAF2-mediated NF-kappaB activation via IKKbeta. In addition, HCV core protein associates with TNF-R1-TRADD-TRAF2 signaling complex, resulting in synergistically activation of NF-kappaB induced by TNF-alpha. Thus, these observations indicate that HCV core protein may play an important role in the regulation of the cellular inflammatory and immune responses through NF-kappaB. |
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