The retinoid X receptor (RXR)[1] is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance,[2][3] and 9-cis-13,14-dihydroretinoic acid, which may be an endogenous mammalian RXR-selective agonist.[4]Bexarotene is the only specific activator of the RXRs which does not activate retinoic acid receptors.[5]
RXR heterodimerizes with multiple nuclear receptors including CAR, FXR, LXR, PPAR,[6]PXR, RAR, TR, ER and VDR. RXRs are permissive co-receptors as only one of six alleles is needed for normal development and health.[7] Given this, it is difficult to extrapolate whether the RXR pathway has its own endogenous activity driven by 9-cis retinoic acid species or whether it merely participates in other pathways, predominantly the retinoic nuclear receptor pathway. Genomic knockout of the RXRs results in obesity resistance[8] while bexarotene treatment causes severe hypothyroidism,[9] suggesting that the RXR pathway functions at least to regulate the thyroid hormone receptor pathway.
As with other type II nuclear receptors, the RXR heterodimer in the absence of ligand is bound to hormone response elements complexed with corepressor protein. Binding of agonist ligands to RXR results in dissociation of corepressor and recruitment of coactivator protein, which, in turn, promotes transcription of the downstream target gene into mRNA and eventually protein.
References
↑ Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, etal. (December 2006). "International Union of Pharmacology. LXIII. Retinoid X receptors". Pharmacological Reviews. 58 (4): 760–772. doi:10.1124/pr.58.4.7. PMID17132853. S2CID1476000.
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