Essential role of BCL9-2 in the switch between β-catenin's adhesive and transcriptional functions
Essential role of BCL9-2 in the switch between β-catenin's adhesive and transcriptional functions
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DOI：
10.1101/gad.317604
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发表时间：
2004-09-15
影响因子：
10.5
通讯作者：
Birchmeier, W
中科院分区：
文献类型：
--
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
β-连环蛋白控制钙粘附素介导的细胞黏附和Wnt靶基因的激活。我们在这里证明了β-连环蛋白结合蛋白BCL9-2，人类原癌基因产物BCL9的同系物，诱导未转化细胞的上皮-间充质转变，并增加β-连环蛋白依赖的转录。BCL9-2在癌细胞中的RNA干扰诱导上皮表型，并将β-连环素从细胞核转移到细胞膜。β-连环蛋白的黏附功能和转录功能之间的转换受β-连环蛋白酪氨酸142的磷酸化调节，这有利于BCL9-2的结合，并排除了与α-连环蛋白的相互作用。在斑马鱼胚胎发育过程中，BCL9-2参与WNT8信号通路，调节中胚层发育。
beta-Catenin controls both cadherin-mediated cell adhesion and activation of Wnt target genes. We demonstrate here that the beta-catenin-binding protein BCL9-2, a homolog of the human proto-oncogene product BCL9, induces epithelial-mesenchymal transitions of nontransformed cells and increases beta-catenin-dependent transcription. RNA interference of BCL9-2 in carcinoma cells induces an epithelial phenotype and translocates beta-catenin from the nucleus to the cell membrane. The switch between beta-catenin's adhesive and transcriptional functions is modulated by phosphorylation of Tyr 142 of beta-catenin, which favors BCL9-2 binding and precludes interaction with alpha-catenin. During zebrafish embryogenesis, BCL9-2 acts in the Wnt8-signaling pathway and regulates mesoderm patterning.