Hepatitis C virus core inhibits the fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes
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- Title
- Hepatitis C virus core inhibits the fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes
- Authors
- Yang, SH; Lee, CG; Lee, CW; Choi, EJ; Yoon, SK; Ahn, KS; Sung, YC
- Date Issued
- 2002-06-30
- Publisher
- SPRINGER-VERLAG SINGAPORE PTE LTD
- 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.
- Keywords
- ASK1; core; Fas; hepatitis C virus; p38; NECROSIS-FACTOR-ALPHA; ICE/CED-3 FAMILY PROTEASES; PROTEIN-KINASE; MAP KINASE; TRANSDUCTION PATHWAY; CELL-DEATH; T-CELLS; APOPTOSIS; LIVER; SURVIVAL
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/19010
- ISSN
- 1016-8478
- Article Type
- Article
- Citation
- MOLECULES AND CELLS, vol. 13, no. 3, page. 452 - 462, 2002-06-30
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