SMRT recruitment by PPARgamma is mediated by specific residues located in its carboxy-terminal interacting domain.
SMRT recruitment by PPARgamma is mediated by specific residues located in its carboxy-terminal interacting domain.
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PPARgamma 的 SMRT 募集是由位于其羧基末端相互作用结构域中的特定残基介导的。
DOI：
10.1016/j.mce.2006.08.004
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发表时间：
2006
影响因子：
4.1
通讯作者：
Cohen,RonaldN
中科院分区：
文献类型：
--
作者：
Sutanto,MariaM;Symons,MelissaS;Cohen,RonaldN
类维生素A和甲状腺激素受体（SMRT）的沉默介体已被证明在脂肪形成和PPARγ转录活性中起重要作用。SMRT包含两个相互作用的结构域，介导与核受体的相互作用。有趣的是，SMRT通过其C-末端相互作用结构域被募集到PPARγ，并且近端相互作用结构域的突变不干扰通过PPARγ的募集。为了理解远端相互作用结构域如何介导PPARγ的募集，我们现在将该结构域中的残基突变为近端结构域中发现的相应氨基酸。我们发现，在这个远端结构域的特定残基是至关重要的相互作用与PPARγ，但不是一个相关的受体，RARα。此外，相互作用结构域序列不同的天然SMRT亚型对PPARγ的募集作用与RARα不同。这些数据表明，PPARγ和RARα通过不同的机制与SMRT相互作用。这些差异将是重要的配体的设计，导致特定模式的核受体募集辅阻遏物。
The silencing mediator of retinoid and thyroid hormone receptors (SMRT) has been shown to play an important role in adipogenesis and PPARγ transcriptional activity. SMRT contains two interacting domains that mediate interactions with nuclear receptors. Interestingly, SMRT is recruited to PPARγ via its C-terminal interacting domain, and mutation of the proximal interacting domain does not interfere with recruitment via PPARγ. To understand how the distal interacting domain mediates recruitment by PPARγ, we have now mutated residues in this domain to the corresponding amino acids found in the proximal domain. We show that specific residues in this distal domain are vital for interactions with PPARγ, but not for a related receptor, RARα. Furthermore, naturally-occuring SMRT isoforms that differ in interacting domain sequences have different effects on PPARγ as opposed to RARα recruitment. These data suggest that PPARγ and RARα interact with SMRT via distinct mechanisms. These differences will be important as ligands are designed that lead to specific patterns of nuclear receptor recruitment of corepressors.