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

HARAGUCHI, K ; OHSUGI, M ; ABE, Y ; SEMBA, K ; AKIYAMA, T ; YAMAMOTO, T

Oncogene, 2008-01, Vol.27 (3), p.274-284 [Periódico revisado por pares]

Basingstoke: Nature Publishing

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Título:
Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin
Autor: HARAGUCHI, K ; OHSUGI, M ; ABE, Y ; SEMBA, K ; AKIYAMA, T ; YAMAMOTO, T
Assuntos: Binding proteins ; Biological and medical sciences ; Carcinogenesis ; Cell differentiation ; Cell fate ; Cell physiology ; Cell proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cellular signal transduction ; Embryogenesis ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genetic aspects ; Glycogen ; Glycogen synthase kinase 3 ; Health aspects ; Kinases ; Lymphocytes T ; Molecular and cellular biology ; Phosphorylation ; Physiological aspects ; Proteasomes ; Signal transduction ; Transcription factors ; Wnt protein ; β-Catenin
É parte de: Oncogene, 2008-01, Vol.27 (3), p.274-284
Descrição: 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.
Editor: Basingstoke: Nature Publishing
Idioma: Inglês

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

HARAGUCHI, K ; OHSUGI, M ; ABE, Y ; SEMBA, K ; AKIYAMA, T ; YAMAMOTO, T

Basingstoke: Nature Publishing

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