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. 1993 Oct 15;295 ( Pt 2)(Pt 2):343-6.
doi: 10.1042/bj2950343.

9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway

C Carlberg  1 , J H Saurat, G Siegenthaler
Affiliations

9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway

C Carlberg et al. Biochem J. .

Abstract

The pleiotropic activities of retinoids are mediated by two types of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). All-trans-retinoic acid (RA) transcriptionally activates RARs, but not RXRs, whereas its natural stereoisomer, 9-cis-RA, is the ligand for RXRs. Here, we demonstrate that 9-cis-RA did not transcriptionally activate RARs, whereas in the presence of all-trans-RA the transactivation of RARs was inhibited in a dose-dependent manner by 9-cis-RA. RAR homodimer complexes were destabilized in vitro in the presence of 9-cis-RA. This suggests that 9-cis-RA may be a natural antagonist of all-trans-RA for binding to RAR complexes. The levels of 9-cis-RA may determine by which pathway the transcription of retinoid-responsive genes is modulated.

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