Journal
ONCOGENE
Volume 27, Issue 3, Pages 274-284Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210644
Keywords
Wnt; beta-catenin; GSK-3 beta; Ajuba; phosphorylation
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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.
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