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

Roland Schüle, Pundi Rangarajan, Na Yang, Steven Kliewer, Lynn J. Ransone, Jack Bolado, Inder M. Verma, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

551 Scopus citations

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 (RARα, RARβ, and RARγ) 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 RARa 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 RARα inhibits binding of Jun protein to target DNA. These data suggest that the RARα may form a nonproductive complex with c-Jun and provides a simple mechanism by which retinoic acid may limit cell growth and possibly malignant progression.

Original languageEnglish (US)
Pages (from-to)6092-6096
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number14
DOIs
StatePublished - Jul 15 1991

Keywords

  • Oncogenes
  • Steroid receptors
  • Transcription
  • Vitamin A

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Retinoic acid is a negative regulator of AP-1-responsive genes'. Together they form a unique fingerprint.

Cite this