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 is likely to be the major endogenous mammalian RXR-selective agonist.[4]
In a novel review publication, this 9-cis-13,14-dihydroretinoic acid was shown to be a metabolite not originating from the known vitamin A (vitamin A1) pathway and its nutritional precursors all-trans-retinol (vitamin A (vitamin A1) or all-trans-beta-carotene (provitamin A (provitamin A1)).[5]
An independent pathway for generating this endogenous RXR-ligand 9-cis-13,14-dihydroretinoic acid from 9-cis-13,14-dihydroretinol present in food source and named vitamin A5 or alternatively via provitamin A5 has been suggested[5] as the first novel vitamin identified since 1948, cobalamin / vitamin B12.
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 subfamily 1 nuclear receptors including CAR, FXR, LXR, PPAR,[6] PXR, RAR, TR, and VDR.
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.
See also
References
- ^ Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H (2006). "International Union of Pharmacology. LXIII. Retinoid X receptors". Pharmacol Rev. 58 (4): 760–72. doi:10.1124/pr.58.4.7. PMID 17132853. S2CID 1476000.
- ^ de Lera AR, Krezel W, Rühl R (2016). "An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!". ChemMedChem. 11 (10): 1–12. doi:10.1002/cmdc.201600105. PMID 27151148. S2CID 269196.
- ^ Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P, Levin AA (1993). "Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids". Proc Natl Acad Sci USA. 90 (1): 30–4. 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, Wietrzych-Schindler M, Álvarez S, Szklenar M, Nagy L, de Lera AR, Krężel W (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.
- ^ a b Rühl R, Krężel W, de Lera AR (2018). "9-cis-13,14-Dihydroretinol, a new endogenous mammalian ligand of the retinood X receptor and the active ligand of a potential new vitamin category: vitamin A5". Nutr. Rev. 76 (12): 929–941. doi:10.1093/nutrit/nuy057. PMID 30358857.
- ^ Plutzky J (April 2011). "The PPAR-RXR transcriptional complex in the vasculature: energy in the balance". Circ. Res. 108 (8): 1002–16. doi:10.1161/CIRCRESAHA.110.226860. PMID 21493923.
External links
- Retinoid+X+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)