Is 9-cis-retinoic acid the endogenous ligand for the retinoic acid-X receptor?
Specific proteins in the nucleus act as transcription factors upon activation through binding of small molecules (all-trans-retinoic acid, thyroid hormone, vitamin D, and others). The activated (liganded) receptors bind to specific DNA elements as heterodimers, each in combination with the retinoic acid-X receptor (RXR). 9-Cis-retinoic acid binds to RXR with high affinity and activates it. Though 9-cis-retinoic acid was initially found in animal tissues, in later work 9-cis-retinoic acid could not be detected. A search for a ligand for RXR in tissues showed that unsaturated fatty acids, particularly linoleic, linolenic, and docosahexaenoic acids, bound to and activated RXR as specific ligands, although with low affinity. A critical experiment demonstrated that, at least in developing mouse skin, 9-cis-retinoic acid is not the ligand for RXR.
Wolf
George
G
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, USA.
D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D008024:Ligands; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism*; D014157:Transcription Factors; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin