Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann B G, Kemler R
Department of Molecular Embryology, Max-Planck Institute for Immunobiology, Freiburg, Germany.
Mech Dev. 1996 Sep;59(1):3-10. doi: 10.1016/0925-4773(96)00597-7.
Vertebrate beta-catenin and Drosophila Armadillo share structural similarities suggesting that beta-catenin, like Armadillo, has a developmental signaling function. Both proteins are present as components of cell adherens junctions, but accumulate in the cytoplasm upon Wingless/Wnt signaling. beta-Catenin has axis-inducing properties like Wnt when injected into Xenopus blastomeres, providing evidence for participation of beta-catenin in the Wnt-pathway, but until now no downstream targets for beta-catenin have been identified. Here we demonstrate that beta-catenin binds to the HMG-type transcription factor lymphoid enhancer factor-1 (LEF-1), resulting in a nuclear translocation of beta-catenin both in cultured mouse cells and after ectopic expression of LEF-1 in two-cell mouse embryos. LEF-1/beta-catenin complexes bind to the promoter region of the E-cadherin gene in vitro, suggesting that this interaction could regulate E-cadherin transcription. As shown for beta-catenin, ectopic expression of LEF-1 in Xenopus embryos caused duplication of the body axis, indicating a regulatory role for a LEF-1-like molecule in dorsal mesoderm formation.
脊椎动物的β-连环蛋白与果蝇的犰狳蛋白在结构上有相似之处，这表明β-连环蛋白与犰狳蛋白一样，具有发育信号功能。这两种蛋白都是细胞黏附连接的组成成分，但在无翅型/翼状螺旋转录因子信号作用下会在细胞质中积累。当注射到非洲爪蟾卵裂球中时，β-连环蛋白具有与翼状螺旋转录因子类似的轴诱导特性，这为β-连环蛋白参与翼状螺旋转录因子信号通路提供了证据，但到目前为止，尚未确定β-连环蛋白的下游靶点。在此我们证明，β-连环蛋白与HMG型转录因子淋巴细胞增强因子-1（LEF-1）结合，导致β-连环蛋白在培养的小鼠细胞中以及在双细胞期小鼠胚胎中异位表达LEF-1后发生核转位。LEF-1/β-连环蛋白复合物在体外与E-钙黏蛋白基因的启动子区域结合，这表明这种相互作用可能调节E-钙黏蛋白的转录。正如β-连环蛋白所示，在非洲爪蟾胚胎中异位表达LEF-1会导致体轴重复，这表明类似LEF-1的分子在背侧中胚层形成中具有调节作用。
