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PMID: 8134379 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3.

Wang XW, Forrester K, Yeh H, Feitelson MA, Gu JR, Harris CC

Abstract

Chronic active hepatitis caused by infection with hepatitis B virus, a DNA virus, is a major risk factor for human hepatocellular carcinoma. Since the oncogenicity of several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene products, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX complexes with the wild-type p53 protein and inhibits its sequence-specific DNA binding in vitro. HBX expression also inhibits p53-mediated transcriptional activation in vivo and the in vitro association of p53 and ERCC3, a general transcription factor involved in nucleotide excision repair. Therefore, HBX may affect a wide range of p53 functions and contribute to the molecular pathogenesis of human hepatocellular carcinoma.

MeSH Terms
Cell Line DNA/metabolism DNA-Binding Proteins/metabolism Drosophila Proteins Humans Mutation Protein Binding Trans-Activators/metabolism Transcription Factors/metabolism Transcriptional Activation Tumor Suppressor Protein p53/antagonists & inhibitors,genetics,metabolism Viral Regulatory and Accessory Proteins
Chemicals
DNA-Binding Proteins Drosophila Proteins Trans-Activators Transcription Factors Tumor Suppressor Protein p53 Viral Regulatory and Accessory Proteins hepatitis B virus X protein hay protein, Drosophila DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang X W
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Forrester K
Yeh H
Feitelson M A
Gu J R
Harris C C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-03-15
Pages
2230-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43344
Subset
IM
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