Kaiso/p120-Catenin and TCF/β-Catenin Complexes Coordinately Regulate Canonical Wnt Gene Targets

Summaryβ-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to β-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased β-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of β-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and β-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis