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

• Published in: Nature (London) Vol. 355; no. 6358; pp. 359 - 361
• Main Authors: Levin, Arthur A, Sturzenbecker, Laurie J, Kazmer, Sonja, Bosakowski, Thomas, Huselton, Christine, Allenby, Gary, Speck, Jeffrey, ratzeisen, Cl, Rosenberger, Michael, Lovey, Allen, Grippo, Joseph F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 23.01.1992
• Subjects: Animals; Base Sequence; Binding, Competitive; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Cell Line; Cell Nucleus - metabolism; Cell receptors; Cell structures and functions; Chromatography, High Pressure Liquid; Fundamental and applied biological sciences. Psychology; Humans; Kinetics; Liver - metabolism; Miscellaneous; Molecular and cellular biology; Molecular Sequence Data; Oligodeoxyribonucleotides; Polymerase Chain Reaction - methods; Protein Binding; Receptors, Retinoic Acid; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; RNA, Messenger - genetics; Stereoisomerism; Transcription, Genetic; Transfection; Tretinoin - metabolism; Stereoisomer; Vertebrata; Mammalia; Binding capacity; Ligand; Cell nucleus; Monkey; Primates; Activation; Retinoic acid; Kidney; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/355359a0

Vitamin A (retinol) and its natural derivatives are required for many physiological processes. 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 interaction. RXR alpha is activated by t-RA, yet has little binding affinity for this ligand. t-RA may be converted to a more proximate ligand that directly binds and activates RXR alpha, 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 RXR alpha. These results suggest a new role for isomerization in the physiology of natural retinoids.