α-Catenin Inhibits β-Catenin Signaling by Preventing Formation of a β-Catenin·T-cell Factor·DNA Complex

α-Catenin and β-catenin link cadherins to the cytoskeleton at adherens junctions. β-Catenin also associates with members of the T-cell factor (Tcf) family of transcription factors, and mutations in β-catenin lead to activation of Tcf-dependent transcription and increased cell growth. Although the loss of α-catenin expression can also promote cell growth, the role of endogenous α-catenin in β-catenin signaling is unclear. Here we show that loss of α-catenin expression in a colon cancer cell line correlates with increased Tcf-dependent transcription. The presence of α-catenin in colon cancer cell nuclei suggests that it inhibits transcription directly, and, in agreement with this, ectopic expression of α-catenin in the nucleus represses Tcf-dependent transcription. Furthermore, recombinant α-catenin disrupts the interaction between the β-catenin·Tcf complex and DNA. We conclude that α-catenin inhibits β-catenin signaling in the nucleus by interfering with the formation of a β-catenin·Tcf·DNA complex.