Carlberg C, Saurat J H, Siegenthaler G
Clinique de Dermatologie, Hôpital Cantonal universitaire, Genève, Switzerland.
Biochem J. 1993 Oct 15;295 ( Pt 2)(Pt 2):343-6. doi: 10.1042/bj2950343.
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.
类视黄醇的多效性活动由两种核受体介导，即视黄酸受体（RARs）和类视黄醇X受体（RXRs）。全反式视黄酸（RA）通过转录激活RARs，但不激活RXRs，而其天然立体异构体9-顺式视黄酸是RXRs的配体。在此，我们证明9-顺式视黄酸不会通过转录激活RARs，而在全反式视黄酸存在的情况下，9-顺式视黄酸会以剂量依赖的方式抑制RARs的反式激活。在体外，9-顺式视黄酸存在时RAR同源二聚体复合物不稳定。这表明9-顺式视黄酸可能是全反式视黄酸与RAR复合物结合的天然拮抗剂。9-顺式视黄酸的水平可能决定视黄醇反应性基因的转录通过哪条途径被调节。
