Hepatitis C virus core inhibits the Fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes

Se Hwan Yang, Chang Geun Lee, Chang Woo Lee, Eui Ju Choi, Seung Kew Yoon, Kwang Seog Ahn, Young Chul Sung

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    The p38 mitogen activated kinase (MAPK) signaling pathway plays an essential role in regulating many cellular processes, including inflammation, cell differentiation, and cell death. Here, we report that the hepatitis C virus (HCV) core inhibits the Fas-mediated p38 signaling pathway. The Fas-mediated p38 activation is suppressed in core-expressing HepG2 cell lines, as well as in the hepatocytes of transgenic mice. In addition, core protein blocked the Fas-mediated activation of apoptosis signal-regulating kinase 1 (ASK1), a major upstream MAPKKK of p38. Treatment of a specific p38 inhibitor (SB203580) or overexpression of a kinase-defective mutant, ASK1 (K709R), promoted Fas-mediated cell death in HepG2 cells. This suggests that the p38 and ASK1 activation is required for cell survival against Fas-mediated cell death. In addition, we observed that the HCV core protein enhances Fas-mediated liver injury and lethality in transgenic mice. Collectively, our findings suggest that the HCV core inhibits the Fas-mediated p38 signaling pathway, which results in accelerated Fas-mediated cell death.

    Original languageEnglish
    Pages (from-to)452-462
    Number of pages11
    JournalMolecules and cells
    Volume13
    Issue number3
    Publication statusPublished - 2002 Jun

    Keywords

    • ASK1
    • Core
    • Fas
    • Hepatitis C Virus
    • p38

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Hepatitis C virus core inhibits the Fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes'. Together they form a unique fingerprint.

    Cite this