Transcriptional repression of the human p53 gene by hepatitis B viral core protein (HBc) in human liver cells.
Hepatitis B virus (HBV) is a causative agent of chronic and acute hepatitis, and is associated with the development of hepatocellular carcinoma (HCC). We demonstrate here that the Hepatitis B viral core protein (HBc) functions as a repressor on the promoter activity of the human p53 gene. The functional analyses of the promoter of the p53 gene by serial deletion, site-directed mutagenesis, and the heterologous promoter system revealed that the promoter activity was repressed through the E2F1-binding site (nucleotides -28 to -8) by HBc. An electrophoretic mobility shift assay (EMSA) showed that the HBc reduced the DNA-binding ability of E2F1 to the binding site of the p53 promoter. The interaction of HBc with E2F1 was also observed by glutathione S-transferase (GST) fusion protein binding assay. Furthermore, HBc represses the expression of the p53 gene in the human liver cell line HepG2. Finally, HBc and HBx synergistically repress both the promoter activity and the expression of the p53 gene in HepG2 cells. These results, together with our previous study, strongly suggest that HBc, like HBx, represses the expression of the human p53 tumor suppressor gene.
Kwon
Jin Ah
JA
School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Rho
Hyune Mo
HM
D001665:Binding Sites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D024202:Electrophoretic Mobility Shift Assay; D016158:Genes, p53 / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D005982:Glutathione Transferase