Mechanism of corepressor binding and release from nuclear hormone receptors
Mechanism of corepressor binding and release from nuclear hormone receptors
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DOI：
10.1101/gad.13.24.3209
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发表时间：
1999-12-15
影响因子：
10.5
通讯作者：
Schwabe, JWR
中科院分区：
文献类型：
--
作者：
Nagy, L;Kao, HY;Schwabe, JWR
转录辅抑制因子SMRT和N-CoR与类视黄酮和甲状腺受体的关联导致基础转录活性的抑制。核受体信号传导的一个关键事件是激素依赖性的辅抑制因子的释放和辅激活因子的募集。生物化学和结构研究已经确定了协同激活蛋白中介导与受体lbd关联的普遍基序。我们在这里报道了SMRT和N-CoR中互补的作用特征基序的身份，这些基序足以进行受体结合和配体诱导释放。有趣的是，该基序包含一个疏水核（Phi xx Phi Phi），类似于在NR共激活子中发现的疏水核。令人惊讶的是，直接参与辅激活因子结合的氨基酸突变破坏了辅抑制因子的结合。这些结果表明激活和抑制之间存在直接的机制联系，通过竞争共同或至少部分重叠的结合位点。
The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies have identified a universal motif in coactivator proteins that mediates association with receptor LBDs. We report here the identity of complementary acting signature motifs in SMRT and N-CoR that are sufficient for receptor binding and ligand-induced release. Interestingly, the motif contains a hydrophobic core (Phi xx Phi Phi) similar to that found in NR coactivators. Surprisingly, mutations in the amino acids that directly participate in coactivator binding disrupt the corepressor association. These results indicate a direct mechanistic link between activation and repression via competition for a common or at least partially overlapping binding site.