Smad2和Smad3通过叉头DNA结合蛋白FAST2对转化生长因子β（TGFβ）依赖性转录进行正向和负向调控。
Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2.
作者信息
Labbé E, Silvestri C, Hoodless P A, Wrana J L, Attisano L
机构信息
Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.
出版信息
Mol Cell. 1998 Jul;2(1):109-20. doi: 10.1016/s1097-2765(00)80119-7.
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, Smad2, 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.
我们鉴定出一种哺乳动物叉头结构域蛋白FAST2，它是TGF-β或激活素信号诱导鹅膏蕈氨酸（gsc）启动子所必需的。FAST2与gsc启动子中的一个序列结合，但FAST2、Smad2和Smad4的DNA结合复合物的有效转录激活和组装需要一个相邻的Smad4位点。Smad3与Smad2密切相关，但抑制gsc启动子的激活。抑制活性由MH1结构域赋予，该结构域与Smad2不同，它与Smad4位点结合。通过竞争这个共享位点，Smad3可能通过改变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，通过该机制Smad2和Smad3对TGF-β/激活素靶基因进行正向和负向调节。
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