Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity.
Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an association between hepatocellular carcinoma (HCC) and HCV infection has been noted. Recent experimental evidence using a cloned genomic region suggests that the putative core protein of HCV has numerous biological properties and is implicated as a viral factor for HCV mediated pathogenesis. WAF1/Cip1/Sid1 (p21) is the prototype of a family of proteins that inhibit cyclin-dependent kinases (CDK) and regulate cell cycle progression in eukaryotic cells. In this study, we have observed that the HCV core protein represses the transcriptional activity of the p21 promoter when tested separately by an in-vitro transient expression assay using murine fibroblasts (NIH3T3), human hepatocellular carcinoma (HepG2), and human cervical carcinoma (HeLa) cells. A deletion analysis of the p21 promoter suggested that the HCV core responsive region is located downstream of the p53 binding site. A gel mobility shift analysis showed that the HCV core protein does not bind directly to p21 regulatory sequences. Thus, the HCV core protein appears to act as an effector in the promotion of cell growth by repressing p21 transcription through unknown cellular factor(s).
Ray
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RB
Division of Infectious Diseases and Immunology, Saint Louis University, MO 63110, USA. rayrb@sluvca.slu.edu
Steele
R
R
Meyer
K
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Ray
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D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006367:HeLa Cells; D016174:Hepacivirus / Q000502:physiology*; D018936:Hepatitis C Antigens / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000378:metabolism*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018936:Hepatitis C Antigens; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D008156:Luciferases; D005982:Glutathione Transferase