Hepatitis B virus transcriptional activators: mechanisms and possible role in oncogenesis.
The hepatitis B virus (HBV) genome encodes a 154 amino acid protein termed X (HBx, hepatitis B x protein), which is a promiscuous transcriptional activator of polymerase II and III promoters. HBx upregulates a wide range of cellular and viral genes and is thought to facilitate viral pregenome and mRNA transcription; however, its precise role in the viral replication cycle remains to be elucidated. The functional mechanisms of HBx appear very complex. It was shown to activate transcription factors AP-1 and NF-kappa B vis cytoplasmic pathways including ras-MAP kinase. In contrast, nuclear HBx is thought to activate the transcriptional machinery directly. A second transcriptional activator protein (Mst, middle s transactivator) is encoded by 3'-truncated preS2/S sequences of integrated HBV DNA, but not by the intact viral gene. HBx and Mst may contribute to the pathogenicity of chronic hepatitis B and are suggested to promote hepatocyte transformation via upregulation of cellular proto-oncogenes. Further, HBx may enhance HBV related carcinogenesis by inactivation of the tumour suppressor gene product p53.
Henkler F
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Department of Virology, Royal Postgraduate Medical School, London, UK.
Koshy
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D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D006509:Hepatitis B / Q000209:etiology* / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000821:virology*; D008392:Marmota; D016328:NF-kappa B / Q000502:physiology; D011519:Proto-Oncogenes / Q000502:physiology; D012589:Sciuridae; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D004279:DNA, Viral; D016328:NF-kappa B; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein