LXR, A NUCLEAR RECEPTOR THAT DEFINES A DISTINCT RETINOID RESPONSE PATHWAY

被引：930
作者：
WILLY, PJ
UMESONO, K
ONG, ES
EVANS, RM
HEYMAN, RA
MANGELSDORF, DJ
机构：
[1] UNIV TEXAS,SW MED CTR,HOWARD HUGHES MED INST,DALLAS,TX 75235
[2] UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235
[3] SALK INST BIOL STUDIES,SAN DIEGO,CA 92186
[4] HOWARD HUGHES MED INST,SAN DIEGO,CA 92186
[5] LIGAND PHARMACEUT INC,SAN DIEGO,CA 92121
来源：
GENES & DEVELOPMENT | 1995年 / 9卷 / 09期
关键词：
RXR; LXR; ORPHAN RECEPTOR; RETINOID RECEPTORS; 9-CIS RETINOIC ACID; METHOPRENE ACID;
D O I：
10.1101/gad.9.9.1033
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
We have identified a new retinoid response pathway through which 9-cis retinoic acid (9cRA) activates transcription in the presence of LXR alpha, a member of the nuclear receptor superfamily. LXR alpha shows a specific pattern of expression in visceral organs, thereby restricting the response to certain tissues. Retinoid trans-activation occurs selectively on a distinct response element termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR alpha in mediating this retinoid response. We provide evidence that the retinoid response on the LXRE is the result of a unique interaction between LXR alpha and endogenous RXR, which, unlike in the RXR/RAR heterodimer, makes RXR competent to respond to retinoids. Thus, the interaction with LXR alpha shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXREs.
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页码：1033 / 1045
页数：13
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