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E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation
S. Orsulic, O. Huber, H. Aberle, S. Arnold, R. Kemler
Journal of Cell Science 1999 112: 1237-1245;

Summary

Beta-catenin is a multifunctional protein found in three cell compartments: the plasma membrane, the cytoplasm and the nucleus. The cell has developed elaborate ways of regulating the level and localization of beta-catenin to assure its specific function in each compartment. One aspect of this regulation is inherent in the structural organization of beta-catenin itself; most of its protein-interacting motifs overlap so that interaction with one partner can block binding of another at the same time. Using recombinant proteins, we found that E-cadherin and lymphocyte-enhancer factor-1 (LEF-1) form mutually exclusive complexes with beta-catenin; the association of beta-catenin with LEF-1 was competed out by the E-cadherin cytoplasmic domain. Similarly, LEF-1 and adenomatous polyposis coli (APC) formed separate, mutually exclusive complexes with beta-catenin. In Wnt-1-transfected C57MG cells, free beta-catenin accumulated and was able to associate with LEF-1. The absence of E-cadherin in E-cadherin-/- embryonic stem (ES) cells also led to an accumulation of free beta-catenin and its association with LEF-1, thereby mimicking Wnt signaling. beta-catenin/LEF-1-mediated transactivation in these cells was antagonized by transient expression of wild-type E-cadherin, but not of E-cadherin lacking the beta-catenin binding site. The potent ability of E-cadherin to recruit beta-catenin to the cell membrane and prevent its nuclear localization and transactivation was also demonstrated using SW480 colon carcinoma cells.

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Journal Articles
E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation
S. Orsulic, O. Huber, H. Aberle, S. Arnold, R. Kemler
Journal of Cell Science 1999 112: 1237-1245;
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