PARP-1 Attenuates Smad-Mediated Transcription

被引：113

作者：

Lonn, Peter ^{[1
]}

van der Heide, Lars P. ^{[1
]}

Dahl, Markus ^{[1
]}

Hellman, Ulf ^{[1
]}

Heldin, Carl-Henrik ^{[1
]}

Moustakas, Aristidis ^{[1
]}

机构：

[1] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden

来源：

MOLECULAR CELL | 2010年 / 40卷 / 04期

基金：

瑞典研究理事会;

关键词：

GROWTH-FACTOR-BETA; DNA-BINDING; MH1; DOMAIN; POLY(ADP-RIBOSE); SEQUENCE;

D O I：

10.1016/j.molcel.2010.10.029

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 versatile cytokine transforming growth factor beta (TGF-beta) regulates cellular growth, differentiation, and migration during embryonic development and adult tissue homeostasis. Activation of TGF-beta receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions and orchestrate transcription. Termination of Smad-activated transcription involves Smad dephosphorylation, nuclear export, or ubiquitin-mediated degradation. In an unbiased proteomic screen, we identified poly(ADP-ribose) polymerase-1 (PARP-1) as a Smad-interacting partner. PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-beta-induced epithelial-mesenchymal transition. Thus, our results identify ADP-ribosylation of Smad proteins by PARP-1 as a key step in controlling the strength and duration of Smad-mediated transcription.

引用

页码：521 / 532

页数：12

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