9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway.
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.
Carlberg
C
C
Clinique de Dermatologie, Hôpital Cantonal universitaire, Genève, Switzerland.
Saurat
J H
JH
Siegenthaler
G
G
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004330:Drosophila; D007536:Isomerism; D014176:Protein Biosynthesis; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D004247:DNA