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

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)274-284
Number of pages11
JournalOncogene
Volume27
Issue number3
DOIs
Publication statusPublished - 2008 Jan 10

Keywords

  • Ajuba
  • GSK-3β
  • Phosphorylation
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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