TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300

被引：444

作者：

Janknecht, R ^{[1
]}

Wells, NJ ^{[1
]}

Hunter, T ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Mol Biol & Virol Lab, La Jolla, CA 92037 USA

来源：

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

基金：

英国惠康基金;

关键词：

CBP; p300; phosphorylation; Smad protein; TGF-beta; transcription;

D O I：

10.1101/gad.12.14.2114

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

TGE-beta and activin induce the phosphorylation and activation of Smad2 and Smad3, but how these proteins stimulate gene transcription is poorly understood. We report that TGF-beta receptor phosphorylation of Smad3 promotes its interaction with, the paralogous coactivators CEP and p300, whereas CBP/p300 binding to non-phosphorylated ted Smad3 or its' oligomerization partner Smad4 is negatively regulated by Smad-intramolecular interactions. Furthermore, p300 and TGP-beta receptor-phosphorylated Smad3 synergistically augment transcriptional activation. Thus, CBP/p300 are important components of activin/TGF-beta signaling and may mediate the antioncogenic functions of Smad2 and Smad4.

引用

页码：2114 / 2119

页数：6

共 36 条

[1]

The CBP co-activator is a histone acetyltransferase [J].

Bannister, AJ ;

Kouzarides, T .

NATURE, 1996, 384 (6610) :641-643

[2]

Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300 [J].

Chen, HW ;

Lin, RJ ;

Schiltz, RL ;

Chakravarti, D ;

Nash, A ;

Nagy, L ;

Privalsky, ML ;

Nakatani, Y ;

Evans, RM .

CELL, 1997, 90 (03) :569-580

[3]

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

[4]

PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP [J].

CHRIVIA, JC ;

KWOK, RPS ;

LAMB, N ;

HAGIWARA, M ;

MONTMINY, MR ;

GOODMAN, RH .

NATURE, 1993, 365 (6449) :855-859

[5]

MOLECULAR-CLONING AND FUNCTIONAL ANAL OF THE ADENOVIRUS E1A-ASSOCIATED 300-KD PROTEIN (P300) REVEALS A PROTEIN WITH PROPERTIES OF A TRANSCRIPTIONAL ADAPTER [J].

ECKNER, R ;

EWEN, ME ;

NEWSOME, D ;

GERDES, M ;

DECAPRIO, JA ;

LAWRENCE, JB ;

LIVINGSTON, DM .

GENES & DEVELOPMENT, 1994, 8 (08) :869-884

[6]

MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma [J].

Eppert, K ;

Scherer, SW ;

Ozcelik, H ;

Pirone, R ;

Hoodless, P ;

Kim, H ;

Tsui, LC ;

Bapat, B ;

Gallinger, S ;

Andrulis, IL ;

Thomsen, GH ;

Wrana, JL ;

Attisano, L .

CELL, 1996, 86 (04) :543-552

[7]

Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain [J].

Gu, W ;

Roeder, RG .

CELL, 1997, 90 (04) :595-606

[8]

DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1 [J].

Hahn, SA ;

Schutte, M ;

Hoque, ATMS ;

Moskaluk, CA ;

daCosta, LT ;

Rozenblum, E ;

Weinstein, CL ;

Fischer, A ;

Yeo, CJ ;

Hruban, RH ;

Kern, SE .

SCIENCE, 1996, 271 (5247) :350-353

[9]

Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4 [J].

Hata, A ;

Lo, RS ;

Wotton, D ;

Lagna, G ;

Massague, J .

NATURE, 1997, 388 (6637) :82-87

[10]

TGF-beta signalling from cell membrane to nucleus through SMAD proteins [J].

Heldin, CH ;

Miyazono, K ;

tenDijke, P .

NATURE, 1997, 390 (6659) :465-471

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