Tsai C C, Kao H Y, Yao T P, McKeown M, Evans R M
Gene Expression Lab, Salk Institute, La Jolla, California 92037, USA.
Mol Cell. 1999 Aug;4(2):175-86. doi: 10.1016/s1097-2765(00)80365-2.
The Drosophila ecdysone receptor (EcR)/ultraspiracle (USP) heterodimer is a key regulator in molting and metamorphoric processes, activating and repressing transcription in a sequence-specific manner. Here, we report the isolation of an EcR-interacting protein, SMRTER, which is structurally divergent but functionally similar to the vertebrate nuclear corepressors SMRT and N-CoR. SMRTER mediates repression by interacting with Sin3A, a repressor known to form a complex with the histone deacetylase Rpd3/HDAC. Importantly, we identify an EcR mutant allele that fails to bind SMRTER and is characterized by developmental defects and lethality. Together, these results reveal a novel nuclear receptor cofactor that exhibits evolutionary conservation in the mechanism to achieve repression and demonstrate the essential role of repression in hormone signaling.
果蝇蜕皮激素受体（EcR）/超气门蛋白（USP）异二聚体是蜕皮和变态过程中的关键调节因子，以序列特异性方式激活和抑制转录。在此，我们报告了一种与EcR相互作用的蛋白SMRTER的分离，其在结构上与脊椎动物核共抑制因子SMRT和N-CoR不同，但在功能上相似。SMRTER通过与Sin3A相互作用介导抑制作用，Sin3A是一种已知与组蛋白去乙酰化酶Rpd3/HDAC形成复合物的抑制因子。重要的是，我们鉴定出一个EcR突变等位基因，该等位基因无法结合SMRTER，并表现出发育缺陷和致死性。这些结果共同揭示了一种新型核受体辅因子，其在实现抑制的机制中表现出进化保守性，并证明了抑制在激素信号传导中的重要作用。
