Details

Autor(en) / Beteiligte

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

Titel

Retinoic Acid is a Negative Regulator of AP-1-Responsive Genes

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1991-07, Vol.88 (14), p.6092-6096

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1991

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 RARα 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.