Hepatitis C virus core protein represses the p21 promoter through inhibition of a TGF-β pathway

Mi Nam Lee, Eun Young Jung, Hyun Jin Kwun, Hong Ki Jun, Dae Yeul Yu, Yung Hyun Choi, Kyung Lib Jang

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The increased proliferation rate of hepatocytes is one of the major risk factors for the development of hepatocellular carcinoma. In this study, we investigated the mechanism by which hepatitis C virus (HCV) core protein represses transcription of the universal cyclin-dependent kinase inhibitor p21 gene in murine fibroblast NIH 3T3 cells. From the transient reporter assays of p2l promoter, we found that the TGF-β-responsive element (TβRE) located between -83 and -74 of the p2l promoter is responsible for the effect. The TGF-β-induced p21 promoter activity was specifically decreased by HCV core protein and in the presence of the inhibitory Smad7 the repression effect was almost completely abolished. Furthermore, HCV core protein stimulated the growth rate of NIH 3T3 cells and could overcome growth arrest by TGF-β but not by butyrate, suggesting that HCV core protein stimulates cell cycle progression by repressing p21 transcription through a TGF-β pathway.

Original languageEnglish (US)
Pages (from-to)2145-2151
Number of pages7
JournalJournal of General Virology
Volume83
Issue number9
DOIs
StatePublished - Sep 2002

All Science Journal Classification (ASJC) codes

  • Virology

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