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
收藏
页码：2153 / 2163
页数：11
相关论文
共 41 条
[1]   T beta RI phosphorylation of Smad2 on Ser(465) and Ser(467) is required for Smad2-Smad4 complex formation and signaling [J].
Abdollah, S ;
MaciasSilva, M ;
Tsukazaki, T ;
Hayashi, H ;
Attisano, L ;
Wrana, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (44) :27678-27685
[2]   Recruitment of p300/CBP in p53-dependent signal pathways [J].
Avantaggiati, ML ;
Ogryzko, V ;
Gardner, K ;
Giordano, A ;
Levine, AS ;
Kelly, K .
CELL, 1997, 89 (07) :1175-1184
[3]  
Candia AF, 1997, DEVELOPMENT, V124, P4467
[4]   BIOCHEMICAL-EVIDENCE FOR THE AUTOPHOSPHORYLATION AND TRANSPHOSPHORYLATION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR KINASES [J].
CHEN, F ;
WEINBERG, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1565-1569
[5]   Smad4 and FAST-1 in the assembly of activin-responsive factor [J].
Chen, X ;
Weisberg, E ;
Fridmacher, V ;
Watanabe, M ;
Naco, G ;
Whitman, M .
NATURE, 1997, 389 (6646) :85-89
[6]   TRANSFORMING GROWTH-FACTOR-BETA INDUCES THE CYCLIN-DEPENDENT KINASE INHIBITOR P21 THROUGH A P53-INDEPENDENT MECHANISM [J].
DATTO, MB ;
LI, Y ;
PANUS, JF ;
HOWE, DJ ;
XIONG, Y ;
WANG, XF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5545-5549
[7]   TGF-beta receptor signaling [J].
Derynck, R ;
Feng, XH .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1997, 1333 (02) :F105-F150
[8]   Intracellular signalling: The Mad way to do it [J].
Derynck, R ;
Zhang, Y .
CURRENT BIOLOGY, 1996, 6 (10) :1226-1229
[9]   Ligand-independent activation of transforming growth factor (TGF) beta signaling pathways by heteromeric cytoplasmic domains of TGF-beta receptors [J].
Feng, XH ;
Derynck, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (22) :13123-13129
[10]   A kinase subdomain of transforming growth factor-beta (TGF-beta) type I receptor determines the TGF-beta intracellular signaling specificity [J].
Feng, XH ;
Derynck, R .
EMBO JOURNAL, 1997, 16 (13) :3912-3923
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