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Originally published In Press as doi:10.1074/jbc.M000578200 on August 2, 2000

J. Biol. Chem., Vol. 275, Issue 44, 34122-34130, November 3, 2000
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Hepatitis C Virus Core Protein Enhances p53 Function through Augmentation of DNA Binding Affinity and Transcriptional Ability*

Motoyuki Otsuka, Naoya KatoDagger , Keng-Hsin Lan, Hideo Yoshida, Jun Kato, Tadashi Goto, Yasushi Shiratori, and Masao Omata

From the Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan

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 p21waf1 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 hTAFII28, 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.

* This work was supported in part by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research (OPSR) of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence of the core protein used in this paper will appear in the DDBJ/EMBL/GenBank nucleotide sequence data bases with the accession number AB037249.

Dagger To whom correspondence should be addressed: Dept. of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: 81-3-3815-5411 (ext. 33056); Fax: 81-3-3814-0021; E-mail: kato-2im@h.u-tokyo.ac.jp.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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