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 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 p21(waf1) RNA was decreased in the HBx-expressing cells and this effect 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) promoter were sufficient to confer HBx responsiveness to a previously non-responsive promoter, we suggested that HBx represses the transcription of p21(waf1) by downregulating the activity of Sp1. Because the tumor repressor p21(waf1) 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 p21(waf1) by HBx might play an important role in a HBV-mediated pathogenesis.
Ahn
J Y
JY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea.
Chung
E Y
EY
Kwun
H J
HJ
Jang
K L
KL
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004247:DNA; D008156:Luciferases