9-CIS RETINOIC ACID STEREOISOMER BINDS AND ACTIVATES THE NUCLEAR RECEPTOR RXR-ALPHA

被引:1230
作者
LEVIN, AA
STURZENBECKER, LJ
KAZMER, S
BOSAKOWSKI, T
HUSELTON, C
ALLENBY, G
SPECK, J
KRATZEISEN, C
ROSENBERGER, M
LOVEY, A
GRIPPO, JF
机构
[1] HOFFMANN LA ROCHE INC,DEPT MED CHEM,NUTLEY,NJ 07110
[2] HOFFMANN LA ROCHE INC,DEPT DRUG METAB,NUTLEY,NJ 07110
关键词
D O I
10.1038/355359a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:359 / 361
页数:3
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