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 journalArticle

26 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 1

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Yang, S. H., Lee, C. G., Lee, C. W., Choi, E. J., Yoon, S. K., Ahn, K. S., & Sung, Y. C. (2002). Hepatitis C virus core inhibits the Fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes. Molecules and Cells, 13(3), 452-462.