The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation

被引：445

作者：

Feng, XH

Zhang, Y

Wu, RY

Derynck, R ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Cell Biol Program, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94143 USA

来源：

GENES & DEVELOPMENT | 1998年 / 12卷 / 14期

关键词：

TGF-beta signaling; Smad; CBP/p300; transcription; PAI-1; promoter;

D O I：

10.1101/gad.12.14.2153

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate with Smad3 in response to TGF-beta. The association of CBP with Smad3 was localized to the carboxyl terminus of Smad3, which is required for transcriptional activation, and a defined segment in CBP. Furthermore, CBP/p300 stimulated both TGF-beta- and Smad-induced transcription in a Smad4/DPC4-dependent fashion. Smad3 transactivation and TGF-beta-induced transcription were inhibited by expressing E1A, which interferes with CBP functions. The coactivator functions and physical interactions of Smad4 and CBP/p300 with Smad3 allow a model for the induction of gene expression in response to TGF-beta.

引用

页码：2153 / 2163

页数：11

共 41 条

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