A Smad transcriptional corepressor

被引：490

作者：

Wotton, D ^{[1
]}

Lo, RS ^{[1
]}

Lee, S ^{[1
]}

Massagué, J ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, Cell Biol Program, New York, NY 10021 USA

来源：

CELL | 1999年 / 97卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S0092-8674(00)80712-6

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：

Following TGF beta receptor-mediated phosphorylation and association with Smad4, Smad2 moves into the nucleus, binds to target promoters in association with DNA-binding cofactors, and recruits coactivators such as p300/CBP to activate transcription. We identified the homeodomain protein TGIF as a Smad2-binding protein and a repressor of transcription. A TGF beta-activated Smad complex can recruit TGIF and histone deacetylases (HDACs) to a Smad target promoter, repressing transcription. Thus, upon entering the nucleus, a Smad2-Smad4 complex may interact with coactivators, forming a transcriptional activation complex, or with TGIF and HDACs, forming a transcriptional repressor complex. Formation of one of these two mutually exclusive complexes is determined by the relative levels of Smad corepressors and coactivators within the cell.

引用

页码：29 / 39

页数：11

共 73 条

[41] Even-skipped represses transcription by binding TATA binding protein and blocking the TFIID-TATA box interaction [J].

Li, C ;

Manley, JL .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (07) :3771-3781

[42]

Liu B, 1999, MOL CELL BIOL, V19, P424

[43] Dual role of the Smad4/DPC4 tumor suppressor in TGF beta-inducible transcriptional complexes [J].

Liu, F ;

Pouponnot, C ;

Massague, J .

GENES & DEVELOPMENT, 1997, 11 (23) :3157-3167

[44] A human Mad protein acting as a BMP-regulated transcriptional activator [J].

Liu, F ;

Hata, A ;

Baker, JC ;

Doody, J ;

Carcamo, J ;

Harland, RM ;

Massague, J .

NATURE, 1996, 381 (6583) :620-623

[45] The L3 loop:: a structural motif determining specific interactions between SMAD proteins and TGF-β receptors [J].

Lo, RS ;

Chen, YG ;

Shi, YG ;

Pavletich, NP ;

Massagué, J .

EMBO JOURNAL, 1998, 17 (04) :996-1005

[46] Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2 [J].

Macías-Silva, M ;

Hoodless, PA ;

Tang, SJ ;

Buchwald, M ;

Wrana, JL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (40) :25628-25636

[47] MADR2 is a substrate of the TGF beta receptor and its phosphorylation is required for nuclear accumulation and signaling [J].

MaciasSilva, M ;

Abdollah, S ;

Hoodless, PA ;

Pirone, R ;

Attisano, L ;

Wrana, JL .

CELL, 1996, 87 (07) :1215-1224

[48] TGF-β signal transduction [J].

Massagué, J .

ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :753-791

[49] Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase [J].

Nagy, L ;

Kao, HY ;

Chakravarti, D ;

Lin, RJ ;

Hassig, CA ;

Ayer, DE ;

Schreiber, SL ;

Evans, RM .

CELL, 1997, 89 (03) :373-380

[50] Identification of Smad7, a TGF beta-inducible antagonist of TGF-beta signalling [J].

Nakao, A ;

Afrakhte, M ;

Moren, A ;

Nakayama, T ;

Christian, JL ;

Heuchel, R ;

Itoh, S ;

Kawabata, N ;

Heldin, NE ;

Heldin, CH ;

tenDijke, P .

NATURE, 1997, 389 (6651) :631-635

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