Retinoic acid receptor

Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X-receptors (RXRs) to regulate cell growth, differentiation and apoptosis of cells (Benbrook DM 2014).

Retinoic acid receptors belong to the 1B group of nuclear receptors and are closely related to thyroid hormone receptors (TR; NR1A) (Allenby G et al. 1993). There are 3 genes, RARα, β and γ which are encoded by the 3 isoforms RAR-α, RAR-beta and RAR-gamma. The RAR isoforms have 10 splice variants: 4 for RAR-alpha, 4 for RAR-beta and 2 for RAR-gamma.

As with other nuclear receptors, RAR heterodimerizes with RXR, and in the absence of ligands, the RAR/RXR dimer binds to hormone reactive elements known as retinoic acid reactive elements (RAREs), which are complexed with the corepressor protein.

The role of multiprotein complexes (core compressors, CoRs and coactivators, CoAs), which specify the transcriptional activity of RARs and RXRs and other NRs, illustrates the crucial role of NR-induced chromatin formation. The retinoic acid receptors (RAR) bind to two retinoids:

the all-trans retinoic acid and

the 9-cis retinoic acid.

Due to their regulatory potential, RARs play an important role in a variety of diseases. In this respect, a large number of RAR- and RXR-selective ligands, some of which are agonistically and some antagonistically active, have been studied. In the meantime, corresponding structural and functional analyses have provided deep insights into the molecular basis of the ligand action.

1. Allenby G et al (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 90: 30-34.
2. Benbrook DM (2014) History of retinoic acid receptors.
   Subcell Biochem 70:1-20.
3. le Maire A et al (2012) Retinoid receptors and therapeutic applications of RAR/RXR modulators. Curr Top Med Chem 12:505-527.