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 journalArticle

480 Citations (Scopus)

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
StatePublished - Jul 15 1991

Fingerprint

Retinoic Acid Receptors
Transcription Factor AP-1
Tretinoin
Genes
Collagenases
Retinoid X Receptors
DNA
Retinoids
Electrophoretic Mobility Shift Assay
Transcriptional Activation
Transfection
Carrier Proteins
Down-Regulation
Binding Sites
Growth

Keywords

  • Oncogenes
  • Steroid receptors
  • Transcription
  • Vitamin A

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Schüle, R., Rangarajan, P., Yang, N., Kliewer, S., Ransone, L. J., Bolado, J., ... Evans, R. M. (1991). Retinoic acid is a negative regulator of AP-1-responsive genes. Proceedings of the National Academy of Sciences of the United States of America, 88(14), 6092-6096.

Retinoic acid is a negative regulator of AP-1-responsive genes. / Schüle, Roland; Rangarajan, Pundi; Yang, Na; Kliewer, Steven; Ransone, Lynn J.; Bolado, Jack; Verma, Inder M.; Evans, Ronald M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 14, 15.07.1991, p. 6092-6096.

Research output: Contribution to journalArticle

Schüle, R, Rangarajan, P, Yang, N, Kliewer, S, Ransone, LJ, Bolado, J, Verma, IM & Evans, RM 1991, '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, pp. 6092-6096.
Schüle, Roland ; Rangarajan, Pundi ; Yang, Na ; Kliewer, Steven ; Ransone, Lynn J. ; Bolado, Jack ; Verma, Inder M. ; Evans, Ronald M. / Retinoic acid is a negative regulator of AP-1-responsive genes. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 14. pp. 6092-6096.
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