Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the forkhead DNA-Binding protein FAST2
Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the forkhead DNA-Binding protein FAST2
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DOI：
10.1016/s1097-2765(00)80119-7
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发表时间：
1998-07-01
期刊：
影响因子：
16
通讯作者：
Attisano, L
中科院分区：
文献类型：
--
作者：
Labbe, E;Silvestri, C;Attisano, L
我们确定了哺乳动物叉头结构域蛋白，FAST 2，这是所需的诱导类鹅（gsc）启动子的TGF β或激活素信号。FAST 2与gsc启动子中的序列结合，但FAST 2、Smad 3和Smad 4的DNA结合复合物的有效转录激活和组装需要相邻的Smad 4位点。Smad 3与Smad 2密切相关，但抑制gsc启动子的激活。抑制活性由MH 1结构域赋予，与Smad 2不同，MH 1结构域与Smad 4位点结合。通过竞争这个共享位点，Smad 3可以通过改变DNA结合复合物的构象来阻止转录。因此，我们描述了一种机制，Smad 2和Smad 3积极和消极地调节TGF β/激活素靶基因。
We identify a mammalian forkhead domain protein, FAST2, that is required for induction of the goosecoid (gsc) promoter by TGF beta or activin signaling. FAST2 binds to a sequence in the gsc promoter, but efficient transcriptional activation and assembly of a DNA-binding complex of FAST2, Smad3, and Smad4 requires an adjacent Smad4 site. Smad3 is closely related to Smad2 but suppresses activation of the gsc promoter. Inhibitory activity is conferred by the MH1 domain, which unlike that of Smad2, binds to the Smad4 site. Through competition for this shared site, Smad3 may prevent transcription by altering the conformation of the DNA-binding complex. Thus, we describe a mechanism whereby Smad2 and Smad3 positively and negatively regulate a TGF beta/activin target gene.