Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin

被引：49

作者：

Haraguchi, K. ^{[1
]}

Ohsugi, M. ^{[1
]}

Abe, Y. ^{[1
]}

Semba, K. ^{[2
]}

Akiyama, T. ^{[3
]}

Yamamoto, T. ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Div Oncol, Tokyo 1088639, Japan

[2] Univ Tokyo, Inst Med Sci, Div Cell & Mol Biol, Tokyo 1088639, Japan

[3] Univ Tokyo, Inst Mol & Cell Biol, Lab Mol & Genet Informat, Tokyo 1088639, Japan

来源：

ONCOGENE | 2008年 / 27卷 / 03期

基金：

日本学术振兴会;

关键词：

Wnt; beta-catenin; GSK-3; beta; Ajuba; phosphorylation;

D O I：

10.1038/sj.onc.1210644

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 Wnt signaling pathway is essential for embryonic development and carcinogenesis. Upon Wnt stimulation, beta-catenin is stabilized and associates with T-cell factor or lymphoid enhancing factor, thereby activating transcription of target genes. In the absence of Wnt stimulation, the level of beta-catenin is reduced via glycogen synthase kinase (GSK)-beta b-mediated phosphorylation and subsequent proteasome-dependent degradation. Here, we report the identification of Ajuba as a negative regulator of the Wnt signaling pathway. Ajuba is a member of LIM domain-containing proteins that contribute to cell fate determination and regulate cell proliferation and differentiation. We found that enforced expression of Ajuba destabilized beta-catenin and suppressed target gene expression. Ajuba promoted GSK-3 beta-mediated phosphorylation of beta-catenin by reinforcing the association between beta-catenin and GSK-3 beta. Furthermore, Wnt stimulation induced both accumulation of beta-catenin and destabilization of Ajuba. Our findings suggest that Ajuba is important for regulation of the Wnt signaling pathway.

引用

页码：274 / 284

页数：11

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