Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth.
The phosphoprotein NS5A of hepatitis C virus has recently been suggested to control PKR protein kinase for resistance to interferon. To investigate other functions of NS5A, studies were initiated on the regulation of transcription of important cellular genes and of cell growth by this protein. The results suggested that NS5A protein represses transcription of the cell cycle regulatory gene p21WAF1, while it activates the human proliferating cell nuclear antigen gene in murine fibroblasts and human hepatoma cells. Furthermore, introduction of NS5A into murine fibroblasts (NIH3T3) promoted anchorage-independent growth and tumour formation in nude mice. Thus, NS5A appears to exhibit a role in cell growth regulation.
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D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D017361:Viral Nonstructural Proteins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase