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

Authors
  • Schüle, R
  • Rangarajan, P
  • Yang, N
  • Kliewer, S
  • Ransone, L J
  • Bolado, J
  • Verma, I M
  • Evans, R M
Type
Published Article
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publication Date
Jul 15, 1991
Volume
88
Issue
14
Pages
6092–6096
Identifiers
PMID: 1648728
Source
Medline
License
Unknown

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.

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