alpha-catenin inhibits beta-catenin signaling by preventing formation of a beta-catenin*T-cell factor*DNA complex.

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-catenin. Tcf.DNA complex.
Mesh Terms:
Colonic Neoplasms, Cytoskeletal Proteins, DNA, DNA-Binding Proteins, Humans, Protein Binding, Signal Transduction, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, alpha Catenin, beta Catenin
J Biol Chem
Date: Jul. 21, 2000
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