RAR Activation

Vitamin A and its active derivatives, referred to as retinoids, are non-steroid hormones that play important roles in development, differentiation and homeostasis. The pleiotropic effects of retinoids are mediated by retinoic acid receptor (RARs) and retinoic X receptor (RXRs) which are ligand-activated transcription factors. There are three different RAR isotypes (α, β, and γ) and three RXR isotypes (α, β, and γ). Upon retinoid binding, the RAR/RXR heterodimer undergoes major conformational changes, which cause the release of bound corepressors and expose new binding sites for coactivators that are necessary for initiation of transcription. These complexes bind to the retinoic acid responsive element (RARE) in the promoter regions of the target genes. RARs are also able to repress the activity of other transcription factors such as AP-1 and NF-κB, and therefore have potent anti-proliferative and anti-inflammatory properties.