Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3beta-mediated phosphorylation of beta-catenin.
Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3beta-mediated phosphorylation of beta-catenin.
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发表时间：
2008
期刊：
影响因子：
8
通讯作者：
K. Haraguchi;M. Ohsugi;Y. Abe;K. Semba;T. Akiyama;T. Yamamoto
中科院分区：
文献类型：
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作者：
K. Haraguchi;M. Ohsugi;Y. Abe;K. Semba;T. Akiyama;T. Yamamoto
Wnt信号通路在胚胎发育和肿瘤发生中是必不可少的。在Wnt刺激后，β-连环蛋白被稳定并与T细胞因子或淋巴增强因子结合，从而激活靶基因的转录。在缺乏Wnt刺激的情况下，β-连环蛋白的水平通过糖原合成酶激酶（GSK）-3 β介导的磷酸化和随后的蛋白酶体依赖性降解而降低。在这里，我们报告的鉴定筋骨草作为Wnt信号通路的负调节。筋骨草是一种含有LIM结构域的蛋白质，有助于细胞命运的决定和调节细胞增殖和分化。我们发现，强制表达的筋骨草不稳定β-连环蛋白和抑制靶基因的表达。筋骨草通过加强β-catenin和GSK-3 β之间的结合促进GSK-3 β介导的β-catenin磷酸化。此外，Wnt刺激诱导β-连环蛋白的积累和筋骨草的不稳定。我们的研究结果表明，筋骨草是重要的Wnt信号通路的调节。
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)-3beta-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-3beta-mediated phosphorylation of beta-catenin by reinforcing the association between beta-catenin and GSK-3beta. 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.