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PMID: 1648728 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Retinoic acid is a negative regulator of AP-1-responsive genes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 14 ·1991-07-15 ·Pages 6092-6

Schüle R, Rangarajan P, Yang N, Kliewer S, Ransone LJ, Bolado J, Verma IM, Evans RM

Abstract

We present evidence that retinoic acid can down-regulate transcriptional activation by the nuclear protooncogene c-jun. All three members of the retinoic acid receptor (RAR) subfamily (RAR alpha, RAR beta, and RAR gamma) can repress transcriptional induction of the human collagenase gene or a heterologous promoter that contains the collagenase promoter AP-1-binding site. In contrast, the retinoid X receptor fails to repress Jun/AP-1 activity, demonstrating a significant difference between the two regulatory systems through which retinoids exert their transcriptional control. Analysis of RAR alpha mutants in transfection studies reveals that the DNA-binding domain is important for the inhibition of Jun/AP-1 activity, even though the RAR does not bind the collagenase AP-1 site. Rather, gel-retardation assays reveal that bacterially expressed full-length RAR alpha inhibits binding of Jun protein to target DNA. These data suggest that the RAR alpha may form a nonproductive complex with c-Jun and provides a simple mechanisms by which retinoic acid may limit cell growth and possibly malignant progression.

Related Genes
c-jun
MeSH Terms
Animals Cell Line DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Enzymologic/drug effects HeLa Cells/physiology Microbial Collagenase/genetics Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins c-jun Proto-Oncogenes/drug effects Transcription Factors/genetics,metabolism Transcription, Genetic/drug effects Transcriptional Activation/drug effects Transfection Tretinoin/pharmacology
Chemicals
DNA-Binding Proteins Proto-Oncogene Proteins c-jun Transcription Factors Tretinoin Protein-Tyrosine Kinases Microbial Collagenase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Schüle R
Howard Hughes Medical Institute, La Jolla, CA.
Rangarajan P
Yang N
Kliewer S
Ransone L J
Bolado J
Verma I M
Evans R M
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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.88.14.6092
Published
1991-07-15
Pages
6092-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52028
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.88.14.6092 PMC Full Text View journal details
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