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PMID: 1329088 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 19 ·1992-10-01 ·Pages 9059-63

Huan B, Siddiqui A

Abstract

A retinoid X receptor (RXR) response element was located within the functionally defined hepatitis B virus (HBV) enhancer element. A short segment of the enhancer that contains this region has been shown with genetic analysis to play a key role in the regulation of enhancer function and to represent a major determinant of liver-specific activity. Both the full-length protein and the DNA-binding domain of the liver-specific receptor RXR alpha bound to the putative retinoic acid response element in the HBV enhancer. In vivo, an HBV enhancer-reporter gene construct responds to induction with retinoic acid when cotransfected with an RXR alpha expression vector. A single-base transition (G----A) in the HBV retinoic acid response element leads to a dramatic reduction both in the in vitro binding activity of RXR alpha and the in vivo activity of the HBV enhancer. Thus, retinoic acid and the RXR alpha are implicated as being significant determinants in the liver-specific regulation of HBV gene expression and the resultant disease pathogenesis.

MeSH Terms
Base Sequence Carcinoma, Hepatocellular Cell Nucleus/metabolism DNA-Binding Proteins/genetics,metabolism Enhancer Elements, Genetic/drug effects Genes, Viral Hepatitis B Surface Antigens/genetics Hepatitis B virus/drug effects,genetics Humans Liver Neoplasms Molecular Sequence Data Nuclear Proteins/genetics,metabolism Receptors, Cell Surface/genetics,metabolism Receptors, Retinoic Acid Retinoid X Receptors Trans-Activators/genetics,metabolism Transcription Factors Transcriptional Activation Tretinoin/pharmacology Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Hepatitis B Surface Antigens Nuclear Proteins Receptors, Cell Surface Receptors, Retinoic Acid Retinoid X Receptors Trans-Activators Transcription Factors Tretinoin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Huan B
Department of Microbiology and Immunology, University of Colorado Medical School, Denver 80262.
Siddiqui A
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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
DOI
10.1073/pnas.89.19.9059
Published
1992-10-01
Pages
9059-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50064
Subset
IM
Grants
NCI NIH HHS · CA33135 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.19.9059 PMC Full Text View journal details
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