Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription

Axin antagonizes the developmental effects of Wnt in vertebrates. We show here that Axin simultaneously binds two components of the Wnt pathway, β-catenin and its negative regulator glycogen synthase kinase-3β. In mammalian cells, Axin inhibits Wnt-1 stimulation of β-catenin/lymphoid enhancer factor 1-dependent transcription. Axin also blocks β-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 β-catenin and glycogen synthase kinase-3β, can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.

轴蛋白（Axin）可拮抗脊椎动物体内Wnt信号通路的发育调控效应。本研究证实，轴蛋白可同时结合Wnt信号通路的两种组分：β-连环蛋白（β-catenin）及其负调控因子糖原合酶激酶3β（glycogen synthase kinase-3β）。在哺乳动物细胞中，轴蛋白能够抑制Wnt-1介导的β-连环蛋白/淋巴样增强因子1（lymphoid enhancer factor 1）依赖性转录激活。在携带腺瘤性息肉病（adenomatous polyposis coli，APC）基因突变的结直肠癌细胞中，轴蛋白同样可阻断β-连环蛋白介导的转录过程。上述研究结果表明，轴蛋白可通过与β-连环蛋白及糖原合酶激酶3β形成复合物，阻断Wnt信号通路激活或腺瘤性息肉病基因突变所引发的信号传导。