Behrens J, von Kries J P, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W
Max Delbrück Centre for Molecular Medicine, Berlin, Germany.
Nature. 1996 Aug 15;382(6592):638-42. doi: 10.1038/382638a0.
The cytoplasmic proteins beta-catenin of vertebrates and armadillo of Drosophila have two functions: they link the cadherin cell-adhesion molecules to the cytoskeleton, and they participate in the wnt/wingless signal pathway. Here we show, in a yeast two-hybrid screen, that the architectural transcription factor LEF-1 (for lymphoid enhancer-binding factor) interacts with beta-catenin. In mammalian cells, coexpressed LEF-1 and beta-catenin form a complex that is localized to the nucleus and can be detected by immunoprecipitation. Moreover, LEF-1 and beta-catenin form a ternary complex with DNA that splays an altered DNA bend. Microinjection of LEF-1 into XenoPus embryos induces axis duplication, which is augmented by interaction with beta-catenin. Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus.
脊椎动物的细胞质蛋白β-连环蛋白和果蝇的犰狳蛋白具有两种功能：它们将钙黏蛋白细胞黏附分子与细胞骨架相连，并参与Wnt/无翅信号通路。我们在此通过酵母双杂交筛选表明，结构转录因子LEF-1（淋巴样增强子结合因子）与β-连环蛋白相互作用。在哺乳动物细胞中，共表达的LEF-1和β-连环蛋白形成一种定位于细胞核的复合物，可通过免疫沉淀检测到。此外，LEF-1和β-连环蛋白与DNA形成三元复合物，该复合物呈现出改变的DNA弯曲。将LEF-1显微注射到非洲爪蟾胚胎中会诱导轴重复，与β-连环蛋白的相互作用会增强这种现象。因此，β-连环蛋白通过与LEF-1等转录因子直接相互作用来调节基因表达，为从细胞黏附成分或Wnt蛋白到细胞核的信号传递提供了一种分子机制。
