Smad6 as a transcriptional corepressor
Smad6 as a transcriptional corepressor
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DOI：
10.1074/jbc.275.12.8267
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发表时间：
2000-03-24
影响因子：
4.8
通讯作者：
Cao, X
中科院分区：
文献类型：
--
作者：
Bai, ST;Shi, XM;Cao, X
Smad 6和Smad 7是Smad蛋白的一个亚组，它们拮抗转化生长因子β引起的信号。这两种Smads由转化生长因子β或骨形态发生蛋白（BMP）刺激诱导，与它们活化的I型受体形成稳定的缔合，阻断受体调节的Smads在细胞质中的磷酸化，在这里，我们表明，Smad 6与同源框（Hox）c-8作为转录辅抑制因子相互作用，抑制BMP信号在细胞核中。通过酵母双杂交方法鉴定了Smad 6和Hoxc-8之间的相互作用，并通过细胞中的免疫共沉淀试验进一步证明了这一点。凝胶位移分析表明，Smad 6，而不是Smad 7，相互作用时，与DNA结合的Hoxc-8和Hoxa-9作为异二聚体。更重要的是，Smad 6-Hoxc-8复合物抑制Smad 1与Hoxc-8和Smad 1诱导的转录活性的相互作用。这些数据表明，Smad 6与Hox转录因子相互作用，作为BMP信号通路中负反馈回路的一部分。
Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-beta, These two Smads, induced by transforming growth factor-beta or bone morphogenetic protein (BMP) stimulation, form stable associations with their activated type I receptors, blocking phosphorylation of receptor-regulated Smads in the cytoplasm, Here we show that Smad6 interacts with homeobox (Hox) c-8 as a transcriptional corepressor, inhibiting BMP signaling in the nucleus. The interaction between Smad6 and Hoxc-8 was identified by a yeast two-hybrid approach and further demonstrated by co immunoprecipitation assays in cells. Gel shift assays show that Smad6, but not Smad7, interacts with both Hoxc-8 and Hoxa-9 as a heterodimer when binding to DNA. More importantly, the Smad6-Hoxc-8 complex inhibits interaction of Smad1 with Hoxc-8- and Smad1-induced transcription activity. These data indicate that Smad6 interacts with Hox transcription factors as part of the negative feedback circuit in the BMP signaling pathway.