The nuclear corepressors recognize distinct nuclear receptor complexes.
The nuclear corepressors recognize distinct nuclear receptor complexes.
复制标题
DOI：
10.1210/mend.14.6.0474
复制
发表时间：
2000-06
影响因子：
--
通讯作者：
R. Cohen;Andrew R. Putney;F. Wondisford;A. Hollenberg
中科院分区：
文献类型：
--
作者：
R. Cohen;Andrew R. Putney;F. Wondisford;A. Hollenberg
甲状腺激素受体（TR）和视黄酸受体（RAR）同种型具有在靶反应元件上不存在其配体的情况下沉默基因表达的能力。这种主动阻遏是由辅阻遏物、核受体辅阻遏物（NCoR）和类维生素A和甲状腺激素受体的沉默介导物（SMRT）募集含有组蛋白脱乙酰酶活性的复合物的能力介导的。有趣的是，NCoR和SMRT在其两个核受体相互作用结构域（ID）中存在显著差异，表明它们可能招募具有不同亲和力的受体。此外，受体复合物结合到一个反应元件的作用还没有得到充分的评估，在其招募单独的辅阻遏物的能力。我们在这份报告中表明，近端ID在NCoR和SMRT，共享只有23%的同源性，允许优先识别核受体，这样TR更喜欢招募NCoR，RAR更喜欢招募SMRT，DNA响应元件。然而，在甲状腺激素抵抗综合征中发现的TR突变可以通过改变TRE上形成的复合物（同源二聚体或异源二聚体）来改变辅阻遏物。这些结果表明，辅阻遏物复合物招募可以是核受体和受体复合物特异性。
The thyroid hormone receptor (TR) and retinoic acid receptor (RAR) isoforms have the capacity to silence gene expression in the absence of their ligands on target response elements. This active repression is mediated by the ability of the corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to recruit a complex containing histone deacetylase activity. Interestingly, NCoR and SMRT share significant differences in the their two nuclear receptor-interacting domains (IDs), suggesting that they may recruit receptors with different affinities. In addition, the role of the receptor complex bound to a response element has not been fully evaluated in its ability to recruit separate corepressors. We demonstrate in this report that the proximal ID in NCoR and SMRT, which share only 23% homology, allows preferential recognition of nuclear receptors, such that TR prefers to recruit NCoR, and RAR prefers to recruit SMRT, to DNA response elements. However, mutations in the TR found in the syndromes of resistance to thyroid hormone can change the corepressor recruited by changing the complex (homodimer or heterodimer) formed on the TRE. These results demonstrate that the corepressor complex recruited can be both nuclear receptor- and receptor complex-specific.