Transcriptional repression of p21(waf1) promoter by hepatitis B virus X protein via a p53-independent pathway

The X-gene product of hepatitis B virus (HBx) has been implicated in hepati tis 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 le vel of p21(waf1) RNA was decreased in the HBx-expressing cells and this eff ect was due to the transcriptional repression of the p21(waf1) gene by HBx via a p53-independent pathway. As the Sp1 binding sites of the p21(waf1) pr omoter were sufficient to confer HBx responsiveness to a previously non-res ponsive promoter, we suggested that HBx represses the transcription of p21( waf1) by downregulating the activity of Sp1. Because the tumor repressor p2 1(waf1) protein is a universal inhibitor of cyclin-CDK complexes and DNA re plication that induces cell cycle arrest at the G1-S checkpoint, the repres sion of p21(waf1) by HBx might play an important role in a HBV-mediated pat hogenesis. (C) 2001 Elsevier Science B.V. All rights reserved.