Hepatitis B viral X protein overcomes inhibition of E2F1 activity by pRb on the human Rb gene promoter.
Hepatitis B virus X (HBx) protein is known as an oncogenic transactivator, E2F1 as a positive regulator of the cell cycle, and pRb as a tumor suppressor. Here, we investigated the functional interactions of these proteins on the human Rb promoter. Interestingly, HBx transactivated the Rb promoter cooperatively with E2F1 in HepG2 cells but not in HeLa cells, in which the functions of p53 and pRb are inactive. Combinatorial cotransfection analyses in HepG2 cells showed that HBx overcame the inhibition of E2F1 activity by pRb but not that by p53. Domain analysis showed that aa 47-70 and aa 117-133 of HBx are important for this effect. These results suggest that HBx could inhibit the pRb tumor suppressor and increase E2F1 activity. Our data support the oncogenic potential of HBx, which may cause HBV-infected cells to grow continuously in the development of hepatocellular carcinoma.
School of Biological Sciences, Seoul National University, Seoul, Korea.
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Jeon
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D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016161:Genes, Retinoblastoma; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators / Q000502:physiology*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D010446:Peptide Fragments; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein