Itch E3 ligase-mediated regulation of TGF-β signaling by modulating Smad2 phosphorylation

被引：104

作者：

Bai, YL ^{[1
]}

Yang, C ^{[1
]}

Hu, K ^{[1
]}

Elly, C ^{[1
]}

Liu, YC ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Cell Biol, San Diego, CA 92121 USA

来源：

MOLECULAR CELL | 2004年 / 15卷 / 05期

关键词：

D O I：

10.1016/j.molcel.2004.07.021

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：

Protein ubiquitination has been implicated in the intracellular biochemical events transduced by TGF-beta receptor via different mechanisms including the degradation of Smads or their binding proteins. Here we show that loss of Itch E3 ligase in mouse embryonic fibroblasts (MEFs) results in reduced susceptibility of TGF-beta-induced cell growth arrest and decreased phosphorylation of Smad2, without apparent alteration in protein levels for Smad2, Smad4, and Smad7 in Itch(-/-) MEFs. Itch promotes ubiquitination of Smad2 and augments Smad2 phosphorylation that requires an intact ligase activity of Itch. Moreover, Itch facilitates complex formation between TGF-beta receptor and Smad2 and enhances TGF-beta-induced transcription. This study reveals a previously unrecognized positive TGF-beta signaling pathway via proteolysis-independent ubiquitination.

引用

页码：825 / 831

页数：7

共 28 条

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