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oai:recercat.cat:10230/254782025-12-20T17:04:23Zcom_2072_6col_2072_452952

urn:hdl:10230/25478 Wnt controls the transcriptional activity of Kaiso through CK1ε-dependent phosphorylation of p120-catenin Valle Pérez, Beatriz del Casagolda, David Lugilde, Ero Valls, Gabriela Codina, Montserrat Dave, Natàlia García de Herreros, Antonio Duñach, Mireia Cadherines Proteïnes Fixació Fosforilació Factors de transcripció Wnt signaling p120-catenin Kaiso CK1 phosphorylation p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. In response to Wnt3a, p120-catenin is phosphorylated at Ser268 and Ser269, disrupting its interaction with E-cadherin. Here, we describe that Wnt-induced p120-catenin phosphorylation at Ser268 and Ser269 also enhances its binding to the transcriptional factor Kaiso, preventing Kaiso-mediated inhibition of the β-catenin-Tcf-4 transcriptional complex. Kaiso-mediated repression of this complex is due to its association not only with Tcf-4 but also with β-catenin. Disruption of Tcf-4-Kaiso and β-catenin-Kaiso interactions by p120-catenin not only releases Tcf-4 and β-catenin enabling its mutual association and the formation of the transcriptional complex but also permits Kaiso binding to methylated CpG islands, an interaction that is weakly inhibited by p120-catenin. Consequently, Wnt stimulates Kaiso association to the CDKN2A promoter, which contains CpG sequences, in cells where these sequences are extensively methylated, such as HT-29 M6, an effect accompanied by decreased expression of its gene product. These results indicate that, when released from E-cadherin by Wnt3a-stimulated phosphorylation, p120-catenin controls the activity of the Kaiso transcriptional factor, enhancing its binding to repressed promoters and relieving its inhibition of the β-catenin-Tcf-4 transcriptional complex. 2015-12-18T18:55:36Z 2015-12-18T18:55:36Z 2011 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Journal of cell science. 2011;124(Pt 13):2298-309 © Company of Biologists http://jcs.biologists.org/content/124/13/2298.long DOI 10.1242/jcs.082693 info:eu-repo/semantics/openAccess Company of Biologists