Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription
Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription
复制标题
DOI：
10.1128/mcb.23.24.9081-9093.2003
复制
发表时间：
2003-12-01
影响因子：
5.3
通讯作者：
Feng, XH
中科院分区：
文献类型：
--
作者：
Lin, X;Liang, YY;Feng, XH
Smad 6和Smad 7是由转化生长因子P-Smad信号转导通路负反馈诱导的抑制性Smads。以前认为抑制性Smads与I型受体结合并阻断受体激活的Smads的磷酸化，从而抑制Smad信号传导的起始。相反，很少有研究表明抑制性Smads可能的核功能。在这里，我们提出了令人信服的证据表明，Smad 6抑制骨形态发生蛋白诱导的Id 1转录，通过招募转录辅阻遏物C-末端结合蛋白（CtBP）。一个共识CtBP结合基序，PLDLS，被确定在Smad 6的接头区域。我们的研究结果表明，在基序的突变取消Smad 6结合CtBP，随后其转录抑制活性。我们的结论是，Smad 6和CtBP的核功能和物理相互作用提供了一个新的机制，抑制性Smads的转录调控。
Smad6 and Smad7 are inhibitory Smads induced by transforming growth factor P-Smad signal transduction pathways in a negative-feedback mechanism. Previously it has been thought that inhibitory Smads bind to the type I receptor and block the phosphorylation of receptor-activated Smads, thereby inhibiting the initiation of Smad signaling. Conversely, few studies have suggested the possible nuclear functions of inhibitory Smads. Here, we present compelling evidence demonstrating that Smad6 repressed bone morphogenetic protein-induced Id1 transcription through recruiting transcriptional corepressor C-terminal binding protein (CtBP). A consensus CtBP-binding motif, PLDLS, was identified in the linker region of Smad6. Our findings show that mutation in the motif abolished the Smad6 binding to CtBP and subsequently its repressor activity of transcription. We conclude that the nuclear functions and physical interaction of Smad6 and CtBP provide a novel mechanism for the transcriptional regulation by inhibitory Smads.