Retinoid X receptor

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]

retinoid X receptor alpha
Identifiers
SymbolRXRA
NCBI gene6256
HGNC10477
OMIM180245
RefSeqNM_002957
UniProtP19793
Other data
LocusChr. 9 q34
retinoid X receptor beta
Identifiers
SymbolRXRB
NCBI gene6257
HGNC10478
OMIM180246
RefSeqNM_021976
UniProtP28702
Other data
LocusChr. 6 p21.3
retinoid X receptor gamma
Identifiers
SymbolRXRG
NCBI gene6258
HGNC10479
OMIM180247
RefSeqNM_006917
UniProtP48443
Other data
LocusChr. 1 q22-q23

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
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.


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