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retinoid X receptor beta
retinoid X receptor beta
Identifiers
Symbol	RXRB
NCBI gene	6257
HGNC	10478
OMIM	180246
RefSeq	NM_021976
UniProt	P28702
Other data
Locus	Chr. 6 p21.3
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

retinoid X receptor alpha
retinoid X receptor alpha
Identifiers
Symbol	RXRA
NCBI gene	6256
HGNC	10477
OMIM	180245
RefSeq	NM_002957
UniProt	P19793
Other data
Locus	Chr. 9 q34
Structures
Search for
Structures	Swiss-model
Domains	InterPro

retinoid X receptor gamma

Identifiers

Symbol

Other data

Chr. 1 q22-q23

Search for
Structures	Swiss-model
Domains	InterPro

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 the Retinoic Acid Receptors.^[5]

There are three retinoic X receptors (RXR): RXR-alpha, RXR-beta, and RXR-gamma, encoded by the RXRA, RXRB, RXRG genes, respectively.

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 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, et al. (December 2006). "International Union of Pharmacology. LXIII. Retinoid X receptors". Pharmacological Reviews. 58 (4): 760–772. doi:10.1124/pr.58.4.7. PMID 17132853. S2CID 1476000.
^ de Lera ÁR, Krezel W, Rühl R (May 2016). "An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!". ChemMedChem. 11 (10): 1027–1037. doi:10.1002/cmdc.201600105. PMID 27151148. S2CID 269196.
^ Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, et al. (January 1993). "Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids". Proceedings of the National Academy of Sciences of the United States of America. 90 (1): 30–34. Bibcode:1993PNAS...90...30A. doi:10.1073/pnas.90.1.30. PMC 45593. PMID 8380496.
^ Rühl R, Krzyżosiak A, Niewiadomska-Cimicka A, Rochel N, Szeles L, Vaz B, et al. (June 2015). "9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice". PLOS Genetics. 11 (6): e1005213. doi:10.1371/journal.pgen.1005213. PMC 4451509. PMID 26030625.
^ Panchal MR, Scarisbrick JJ (2015-02-03). "The utility of bexarotene in mycosis fungoides and Sézary syndrome". OncoTargets and Therapy. 8: 367–373. doi:10.2147/OTT.S61308. PMC 4322887. PMID 25678803.
^ Plutzky J (April 2011). "The PPAR-RXR transcriptional complex in the vasculature: energy in the balance". Circulation Research. 108 (8): 1002–1016. doi:10.1161/CIRCRESAHA.110.226860. PMID 21493923.
^ Krezel W, Dupé V, Mark M, Dierich A, Kastner P, Chambon P (August 1996). "RXR gamma null mice are apparently normal and compound RXR alpha +/-/RXR beta -/-/RXR gamma -/- mutant mice are viable". Proceedings of the National Academy of Sciences of the United States of America. 93 (17): 9010–9014. doi:10.1073/pnas.93.17.9010. PMC 38586. PMID 8799145.
^ Haugen BR, Jensen DR, Sharma V, Pulawa LK, Hays WR, Krezel W, et al. (August 2004). "Retinoid X receptor gamma-deficient mice have increased skeletal muscle lipoprotein lipase activity and less weight gain when fed a high-fat diet". Endocrinology. 145 (8): 3679–3685. doi:10.1210/en.2003-1401. PMID 15087432.
^ Esposito M, Amory JK, Kang Y (September 2024). "The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes". The Journal of Experimental Medicine. 221 (9). doi:10.1084/jem.20240519. PMC 11318670. PMID 39133222.