轴蛋白介导的β-连环蛋白与糖原合酶激酶-3β的桥连及β-连环蛋白介导转录的抑制
Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription.
作者信息
Sakanaka C, Weiss J B, Williams L T
机构信息
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0130, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3020-3. doi: 10.1073/pnas.95.6.3020.
Abstract
Axin antagonizes the developmental effects of Wnt in vertebrates. We show here that Axin simultaneously binds two components of the Wnt pathway, beta-catenin and its negative regulator glycogen synthase kinase-3beta. In mammalian cells, Axin inhibits Wnt-1 stimulation of beta-catenin/lymphoid enhancer factor 1-dependent transcription. Axin also blocks beta-catenin-mediated transcription in colon cancer cells that have a mutation in the adenomatous polyposis coli gene. These findings suggest that Axin, by forming a complex with beta-catenin and glycogen synthase kinase-3beta, can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.
摘要
在脊椎动物中，轴抑制蛋白（Axin）拮抗Wnt的发育效应。我们在此表明，轴抑制蛋白同时结合Wnt信号通路的两个组分，β-连环蛋白及其负调控因子糖原合酶激酶-3β。在哺乳动物细胞中，轴抑制蛋白抑制Wnt-1对β-连环蛋白/淋巴样增强因子1依赖性转录的刺激作用。轴抑制蛋白还能阻断在腺瘤性息肉病基因发生突变的结肠癌细胞中β-连环蛋白介导的转录。这些发现表明，轴抑制蛋白通过与β-连环蛋白和糖原合酶激酶-3β形成复合物，可阻断由Wnt或腺瘤性息肉病基因突变所刺激的信号传导。
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