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Title 

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

Authors 

M N LeeE Y JungH J KwunH K JunDae Yeul YuY H ChoiK L Jang

Publisher 

Society for General Microbiology

Issue Date 

2002

Citation 

Journal of General Virology, vol. 83, no. 9, pp. 2145-2151

Keywords 

butyric acidcore proteincyclin dependent kinase inhibitorprotein p21Smad proteintransforming growth factor betaanimal cellcell cyclecell growthcontrolled study

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.

ISSN 

0022-1317

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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