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 an important family of transcription factors that can combine with various nuclear receptors to form a protein dimer, which is often needed for those receptors to perform their functions. It is also a nuclear receptor which is activated by 9-cis retinoic acid, but whether its role as a direct endogenous receptor is important biologically is controversial.[2][3] It can also bind to 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.
Pharmacology
The retinoid X receptors are selectively targeted by certain pharmaceutical retinoids, in particular as part of cancer treatments or to treat severe hand eczema. These including bexarotene and alitretinoin (synthetic 9-cis-retinoic acid), though with the caveat that alitretinoin also has some affinity for the Retinoic Acid Receptors (RARs).[10]
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.
- ↑ "The retinoid X receptors and their ligands". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1821 (1): 21–56. 2012-01-01. doi:10.1016/j.bbalip.2011.09.014. PMID 22020178.
External links
- Retinoid+X+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
 |  |
