Smad4/DPC4 and Smad3 mediate transforming growth factor-β (TGF-β) signaling through direct binding to a novel TGF-β-responsive element in the human plasminogen activator inhibitor-1 promoter

被引：128

作者：

Song, CZ ^{[1
]}

Siok, TE

Gelehrter, TD

机构：

[1] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1998年 / 273卷 / 45期

关键词：

D O I：

10.1074/jbc.273.45.29287

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：

The transforming growth factor-beta (TGF-beta) family of cytokines mediates multiple biological effects by regulating the expression of target genes. The Smad family proteins function as intracellular signal transducers downstream of the receptors to transmit the TGF-beta signal from cell membrane to nucleus. The mechanisms by which Smads mediate transcriptional activation of target genes is largely unknown. Here we report the identification of a novel TGF-beta-responsive element in the human type 1 plasminogen activator inhibitor promoter that is required for mediating strong transcriptional activation of this gene by TGF-beta. Smad3 and Smad4 are incorporated into a TGF-beta inducible complex formed on this element following TGF-beta stimulation of human hepatoma cells. Both Smads and Smad4 bind directly to this TGF-beta-responsive element through their conserved MH1 domains. These results indicate that Smad3 and Smad4 mediate TGF-beta signaling by directly interacting with a specific response element in a physiological target gene.

引用

页码：29287 / 29290

页数：4

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