SMRT isoforms mediate repression and anti-repression of nuclear receptor heterodimers

被引:206
作者
Chen, JD [1 ]
Umesono, K [1 ]
Evans, RM [1 ]
机构
[1] SALK INST BIOL STUDIES, HOWARD HUGHES MED INST, GENE EXPRESS LAB, LA JOLLA, CA 92037 USA
关键词
transcriptional corepressor; dominant negative mutant;
D O I
10.1073/pnas.93.15.7567
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
Transcriptional repression represents an important component in the regulation of cell differentiation and oncogenesis mediated by nuclear hormone receptors, Hormones act to relieve repression, thus allowing receptors to function as transcriptional activators, The transcriptional corepressor SMRT was identified as a silencing mediator for retinoid and thyroid hormone receptors. SMRT is highly related to another corepressor, N-CoR, suggesting the existence of a new family of receptor-interacting proteins. We demonstrate that SMRT is a ubiquitous nuclear protein that interacts with unliganded receptor heterodimers in mammalian cells. Furthermore, expression of the receptor-interacting domain of SMRT acts as an antirepressor, suggesting the potential importance of splicing variants as modulators of thyroid hormone and retinoic acid signaling.
引用
收藏
页码:7567 / 7571
页数:5
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