α-Catenin inhibits β-catenin signaling by preventing formation of a β-catenin T-cell factor DNA complex
α-Catenin inhibits β-catenin signaling by preventing formation of a β-catenin T-cell factor DNA complex
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DOI：
10.1074/jbc.m001929200
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发表时间：
2000-07-21
影响因子：
4.8
通讯作者：
Kypta, RM
中科院分区：
文献类型：
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作者：
Giannini, AL;Vivanco, MDM;Kypta, RM
α-连环蛋白和 β-连环蛋白将钙粘蛋白与粘附连接处的细胞骨架连接起来。 β-连环蛋白还与 T 细胞因子 (Tcf) 转录因子家族的成员相关，β-连环蛋白的突变会导致 Tcf 依赖性转录激活并促进细胞生长。尽管α-连环蛋白表达的丧失也可以促进细胞生长，但内源性α-连环蛋白在β-连环蛋白信号传导中的作用尚不清楚。在这里，我们发现结肠癌细胞系中 α-连环蛋白表达的丧失与 Tcf 依赖性转录的增加相关。结肠癌细胞核中α-连环蛋白的存在表明它直接抑制转录，并且与此一致的是，细胞核中α-连环蛋白的异位表达抑制了Tcf依赖性转录。此外，重组 α-连环蛋白会破坏 β-连环蛋白 Tcf 复合物与 DNA 之间的相互作用。我们得出的结论是，α-连环蛋白通过干扰 β-连环蛋白.Tcf.DNA 复合物的形成来抑制细胞核中的 β-连环蛋白信号传导。
alpha-Catenin and beta-catenin link cadherins to the cytoskeleton at adherens junctions. beta-Catenin also associates with members of the T-cell factor (Tcf) family of transcription factors, and mutations in beta-catenin lead to activation of Tcf-dependent transcription and increased cell growth. Although the loss of alpha-catenin expression can also promote cell growth, the role of endogenous alpha-catenin in beta-catenin signaling is unclear. Here we show that loss of alpha-catenin expression in a colon cancer cell line correlates with increased Tcf-dependent transcription. The presence of alpha-catenin in colon cancer cell nuclei suggests that it inhibits transcription directly, and, in agreement with this, ectopic expression of alpha-catenin in the nucleus represses Tcf-dependent transcription. Furthermore, recombinant alpha-catenin disrupts the interaction between the beta-catenin Tcf complex and DNA. We conclude that alpha-catenin inhibits beta-catenin signaling in the nucleus by interfering with the formation of a beta-cateni.Tcf.DNA complex.