Wnt controls the transcriptional activity of Kaiso through CK1 ε-dependent phosphorylation of p120-catenin

Beatriz del Valle-Perez, David Casagolda, Ero Lugilde, Gabriela Valls, Montserrat Codina, Natàlia Dave, Antonio García de Herreros, Mireia Duñach

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Abstract

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. © 2011. Published by The Company of Biologists Ltd.
Original languageEnglish
Pages (from-to)2298-2309
JournalJournal of Cell Science
Volume124
DOIs
Publication statusPublished - 1 Jul 2011

Keywords

  • CK1 phosphorylation
  • Kaiso
  • P120-catenin
  • Wnt signaling

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    del Valle-Perez, B., Casagolda, D., Lugilde, E., Valls, G., Codina, M., Dave, N., de Herreros, A. G., & Duñach, M. (2011). Wnt controls the transcriptional activity of Kaiso through CK1 ε-dependent phosphorylation of p120-catenin. Journal of Cell Science, 124, 2298-2309. https://doi.org/10.1242/jcs.082693