Transcriptional repression of p21waf1 promoter by hepatitis B virus X protein via a p53-independent pathway

Ji Young Ahn, Eun Young Chung, Hyun Jin Kwun, Kyung Lib Jang

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Abstract

The X-gene product of hepatitis B virus (HBx) has been implicated in hepatitis B virus (HBV)-mediated hepatocellular carcinoma through its ability to induce liver cancer in some transgenic mice and to transactivate a variety of viral and cellular promoters. In this study, we demonstrated that the level of p21waf1 RNA was decreased in the HBx-expressing cells and this effect was due to the transcriptional repression of the p21waf1 gene by HBx via a p53-independent pathway. As the Sp1 binding sites of the p21waf1 promoter were sufficient to confer HBx responsiveness to a previously non-responsive promoter, we suggested that HBx represses the transcription of p21waf1 by downregulating the activity of Sp1. Because the tumor repressor p21waf1 protein is a universal inhibitor of cyclin-CDK complexes and DNA replication that induces cell cycle arrest at the G1-S checkpoint, the repression of p21waf1 by HBx might play an important role in a HBV-mediated pathogenesis.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalGene
Volume275
Issue number1
DOIs
Publication statusPublished - Sep 5 2001

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All Science Journal Classification (ASJC) codes

  • Genetics

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