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RAR-Gamma-RXR-Alpha Degradation

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Description

In response to Retinoic Acid (a metabolite of Vitamin-A (all-trans-Retinol), which affects gene transcription), target genes are regulated by two families of nuclear receptors, the RARs (Retinoic Acid Receptors) and the RXRs (Retinoid X Receptors) that bind as RAR/RXR heterodimers to response elements located in their promoters. The all-trans-Retinoic Acid, the Carboxylic Acid form of Vitamin-A is of biological significance since it is predominant under most physiological situations and explains all of the biological effects of Vitamin-A (Ref.1). Biologically active ligands for the RARs include all-trans-Retinoic Acid, 9-cis-Retinoic Acid among others, yet circulating levels of 9-cis-Retinoic Acid are much lower than those of all-trans-Retinoic Acid and the physiological significance of the isomerization all-trans-Retinoic Acid to 9-cis-Retinoic Acid and vice versa  [...]

References:

1.Retinoid-induced limb malformations.
Lee GS, Kochhar DM, Collins MD.
Curr. Pharm. Des. 2004;10(22):2657-99.
2.Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.
Miano JM, Berk BC.
Circ. Res. 2000 Sep 1;87(5):355-62.
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