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| 9-CIS RETINOIC ACID STEREOISOMER BINDS AND ACTIVATES THE NUCLEAR RECEPTOR RXR-ALPHA |
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| Author(s): LEVIN AA, STURZENBECKER LJ, KAZMER S, BOSAKOWSKI T, HUSELTON C, ALLENBY G, SPECK J, KRATZEISEN C, ROSENBERGER M, LOVEY A, GRIPPO JF |
| Source: NATURE Volume: 355 Issue: 6358 Pages: 359-361 Published: JAN 23 1992 |
| Times Cited: 1,071 References: 35 |
| Abstract: VITAMIN-A (retinol) and its natural derivatives are required for many physiological processes 1-3. 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 interaction 4-10. RXR-alpha 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 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: LEVIN, AA (reprint author), HOFFMANN LA ROCHE INC, DEPT TOXICOL & PATHOL, NUTLEY, NJ 07110 USA |
Addresses:
1. HOFFMANN LA ROCHE INC, DEPT MED CHEM, NUTLEY, NJ 07110 USA
2. HOFFMANN LA ROCHE INC, DEPT DRUG METAB, NUTLEY, NJ 07110 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: HA591 |
| ISSN: 0028-0836 |
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