Biology:Retinoid X receptor
| 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 |
| 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 |
| retinoid X receptor gamma | |
|---|---|
| Identifiers | |
| Symbol | RXRG |
| NCBI gene | 6258 |
| HGNC | 10479 |
| OMIM | 180247 |
| RefSeq | NM_006917 |
| UniProt | P48443 |
| Other data | |
| Locus | Chr. 1 q22-q23 |
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 FDA-approved medication that selectively activates the RXRs while exhibiting negligible activity toward 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 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
- ↑ "International Union of Pharmacology. LXIII. Retinoid X receptors". Pharmacological Reviews 58 (4): 760–772. December 2006. doi:10.1124/pr.58.4.7. PMID 17132853.
- ↑ "An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!". ChemMedChem 11 (10): 1027–1037. May 2016. doi:10.1002/cmdc.201600105. PMID 27151148.
- ↑ "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. January 1993. doi:10.1073/pnas.90.1.30. PMID 8380496. Bibcode: 1993PNAS...90...30A.
- ↑ "9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice". PLOS Genetics 11 (6). June 2015. doi:10.1371/journal.pgen.1005213. PMID 26030625.
- ↑ "The utility of bexarotene in mycosis fungoides and Sézary syndrome". OncoTargets and Therapy 8: 367–373. 3 February 2015. doi:10.2147/OTT.S61308. PMID 25678803.
- ↑ "The PPAR-RXR transcriptional complex in the vasculature: energy in the balance". Circulation Research 108 (8): 1002–1016. April 2011. doi:10.1161/CIRCRESAHA.110.226860. PMID 21493923.
- ↑ "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. August 1996. doi:10.1073/pnas.93.17.9010. PMID 8799145.
- ↑ "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. August 2004. doi:10.1210/en.2003-1401. PMID 15087432.
- ↑ "The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes". The Journal of Experimental Medicine 221 (9). September 2024. doi:10.1084/jem.20240519. PMID 39133222.
External links
- Retinoid+X+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
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