Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability.
Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, and hepatocellular carcinoma. Since there are several reports indicating that some viruses influence the tumor suppressor p53 function, we determined the effects of HCV proteins on p53 function and its mechanism determined by use of a reporter assay. Among seven HCV proteins investigated (core, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only core protein augmented the transcriptional activity of p53 and increased the expression of p21(waf1) protein, which is a major target of p53. Core protein increased both DNA-binding affinity of p53 in electrophoretic morbidity shift assay and transcriptional ability of p53 itself in a reporter assay. The direct interaction between core protein and C terminus of p53 was also shown by glutathione S-transferase fusion protein binding assay. In addition, core protein interacted with hTAF(II)28, a component of the transcriptional factor complex in vivo and in vitro. These results suggest that HCV core protein interacts with p53 and modulates p53-dependent promoter activities during HCV infection.
Otsuka
M
M
Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Kato
N
N
Lan
K
K
Yoshida
H
H
Kato
J
J
Goto
T
T
Shiratori
Y
Y
Omata
M
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014758:Viral Core Proteins / Q000502:physiology*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004279:DNA, Viral; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D005982:Glutathione Transferase