A TRANSCRIPTIONAL CO-REPRESSOR THAT INTERACTS WITH NUCLEAR HORMONE RECEPTORS
A TRANSCRIPTIONAL CO-REPRESSOR THAT INTERACTS WITH NUCLEAR HORMONE RECEPTORS
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DOI：
10.1038/377454a0
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发表时间：
1995-10-05
期刊：
影响因子：
64.8
通讯作者：
EVANS, RM
中科院分区：
文献类型：
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作者：
CHEN, JD;EVANS, RM
由核受体介导的转录沉默在发育、分化和肿瘤发生中具有重要作用（1 - 3）。这种作用的潜在机制尚不清楚，但却是理解激素作用分子基础的关键之一。在此我们鉴定出一种与受体相互作用的因子SMRT，它是类视黄醇受体和甲状腺激素受体的沉默介导因子（辅阻遏物）。SMRT是一种此前未被发现的蛋白质，它与受体在溶液中以及与DNA反应元件结合时的这种关联会因配体而不稳定。它与突变受体的相互作用与其转录沉默活性相关。在体内，SMRT作为一种有效的辅阻遏物发挥作用，并且SMRT的GAL4 DNA结合域融合蛋白表现为GALA依赖性报告基因的一种明确的阻遏物。总之，我们的研究结果确定了一类新的辅因子，它们可能是激素作用的重要介导因子。
TRANSCRIPTIONAL silencing mediated by nuclear receptors is important in development, differentiation and oncogenesis(1-3). The mechanism underlying this effect is unknown but is one key to understanding the molecular basis of hormone action. Here we identify a receptor-interacting factor, SMRT, as a silencing mediator (co-repressor) for retinoid and thyroid-hormone receptors. SMRT is a previously undiscovered protein whose association with receptors both in solution and bound to DNA-response elements is destabilized by ligand. The interaction with mutant receptors correlates with their transcriptional silencing activities. In vivo, SMRT functions as a potent co-repressor, and a GAL4 DNA-binding domain fusion of SMRT behaves as a frank repressor of a GALA-dependent reporter. Together, our results identify a new class of cofactors which may be important mediators of hormone action.