RRC ID 39604
Author Otsuka M, Kato N, Lan K, Yoshida H, Kato J, Goto T, Shiratori Y, Omata M.
Title Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability.
Journal J Biol Chem
Abstract 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.
Volume 275(44)
Pages 34122-30
Published 2000-11-3
DOI 10.1074/jbc.M000578200
PII M000578200
PMID 10924497
MeSH 3T3 Cells Animals Base Sequence COS Cells Cyclin-Dependent Kinase Inhibitor p21 Cyclins / genetics DNA, Viral / metabolism* Glutathione Transferase / genetics Humans Mice Molecular Sequence Data Oligonucleotides Promoter Regions, Genetic Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transcription Factors / metabolism Transcription, Genetic / physiology* Tumor Cells, Cultured Tumor Suppressor Protein p53 / physiology* Viral Core Proteins / physiology*
IF 4.106
Times Cited 129
Human and Animal Cells