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

K. Haraguchi, M. Ohsugi, Y. Abe, K. Semba, T. Akiyama, T. Yamamoto*

*この研究の対応する著者

研究成果: Article査読

44 被引用数 (Scopus)

抄録

The Wnt signaling pathway is essential for embryonic development and carcinogenesis. Upon Wnt stimulation, β-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 β-catenin is reduced via glycogen synthase kinase (GSK)-3β-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 β-catenin and suppressed target gene expression. Ajuba promoted GSK-3β-mediated phosphorylation of β-catenin by reinforcing the association between β-catenin and GSK-3β. Furthermore, Wnt stimulation induced both accumulation of β-catenin and destabilization of Ajuba. Our findings suggest that Ajuba is important for regulation of the Wnt signaling pathway.

本文言語English
ページ(範囲)274-284
ページ数11
ジャーナルOncogene
27
3
DOI
出版ステータスPublished - 2008 1月 10
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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