Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the forkhead DNA-Binding protein FAST2

被引：466

作者：

Labbe, E

Silvestri, C

Hoodless, PA

Wrana, JL

Attisano, L

机构：

[1] Univ Toronto, Dept Anat & Cell Biol, Toronto, ON M5S 1A8, Canada

[2] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada

[3] Hosp Sick Children, Dept Dev Biol, Toronto, ON M5G 1X8, Canada

来源：

MOLECULAR CELL | 1998年 / 2卷 / 01期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/S1097-2765(00)80119-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

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页码：109 / 120

页数：12

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