HBV DNA can bind to P53 protein and influence p53 transactivation in hepatoma cells.
Hepatitis B virus (HBV) may contribute to hepatocarcinogenesis by blocking p53 function. A p53 response element-like binding sequences, TGCCT...TGCCT, was found in HBV genome. To clarify whether HBV DNA can, like some other DNA viruses, bind to P53 protein and form a DNA-protein complex, we used a series of plasmids encoding full-length or mutant HBV or p53 fragments to determine the binding ability of HBV DNA after cotransfected into cells by electrophoretic mobility shift (and supershift) assay. We found that HBV DNA could bind to P53 protein and form DNA-protein complexes in human hepatoma cell lines. Cotransfection with p53 and HBV DNA increased the replication of HBV, CAT activity, tumor cell apoptosis, and cytoplasmic P53 accumulation in the hepatoma cells. In conclusions, our observations suggest that the interaction of HBV and p53 at the levels of protein-protein and DNA-protein, which resulted in inactivation of p53 transactivation.
Qu
Jianhui
J
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Lin
Jing
J
Zhang
Shuhui
S
Zhu
Zhi
Z
Ni
Canrong
C
Zhang
Shunmin
S
Gao
Hengjun
H
Zhu
Minghua
M
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53