Open AccessIs 9‐Cis‐Retinoic Acid the Endogenous Ligand for the Retinoic Acid‐X Receptor?
Author(s) -
Wolf George
Publication year - 2006
Publication title -
nutrition reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.958
H-Index - 150
eISSN - 1753-4887
pISSN - 0029-6643
DOI - 10.1111/j.1753-4887.2006.tb00186.x
Subject(s) - retinoic acid , retinoic acid receptor , retinoid x receptor , retinoic acid receptor gamma , retinoic acid receptor beta , retinoic acid receptor alpha , retinoic acid inducible orphan g protein coupled receptor , biochemistry , retinoid x receptor gamma , receptor , chemistry , biology , ligand (biochemistry) , transcription factor , nuclear receptor , gene
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