9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα

AA Levin, LJ Sturzenbecker, S Kazmer, T Bosakowski… - Nature, 1992 - nature.com
AA Levin, LJ Sturzenbecker, S Kazmer, T Bosakowski, C Huselton, G Allenby, J Speck…
Nature, 1992nature.com
VITAMIN A (retinol) and its natural derivatives are required for many physiological
processes1–3. The activity of retinoids is thought to be mediated by interactions with two
subfamilies of nuclear retinoic acid receptors, RAR and RXR. The RARs bind all-trans
retinoic acid (t-RA) with high affinity and alter gene expression as a consequence of this
direct ligand interaction4–10. RXRα is activated by t-RA, yet has little binding affinity for this
ligand (ref. 11) t-RA may be converted to a more proximate ligand that directly binds and …
Abstract
VITAMIN A (retinol) and its natural derivatives are required for many physiological processes1–3. The activity of retinoids is thought to be mediated by interactions with two subfamilies of nuclear retinoic acid receptors, RAR and RXR. The RARs bind all-trans retinoic acid (t-RA) with high affinity and alter gene expression as a consequence of this direct ligand interaction4–10. RXRα is activated by t-RA, yet has little binding affinity for this ligand (ref. 11) t-RA may be converted to a more proximate ligand that directly binds and activates RXRα, and we have developed a method of nuclear receptor-dependent ligand trapping to test this hypothesis. Here we report the identification of a stereoisomer of retinoic acid, 9-cis retinoic acid, which directly binds and activates RXRα. These results suggest a new role for isomerization in the physiology of natural retinoids.
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