Presenilin-1 interacts with plakoglobin and enhances plakoglobin-Tcf-4 association: Implications for the regulation of β-catenin/Tcf-4-dependent transcription

Imma Raurell, Julio Castaño, Clara Francí, Antonio García De Herreros, Mireia Duñach

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14 Citations (Scopus)

Abstract

Alzheimer disease-linked Presenilin-1 (PS1) is a negative modulator of β-catenin/Tcf-4 activity. However, the mechanism underlying this effect is not well understood. We show here that the effects of PS1 on the activity of this complex in epithelial cells are independent of its γ-secretase activity and its interaction with β-catenin. As presented in this report PS1 also binds plakoglobin with similar affinity as β-catenin, although this interaction does not involve equivalent residues in the two catenins. Moreover, PS1 association with plakoglobin enhances the interaction of this molecule with Tcf-4 and prevents its binding to DNA. These effects were observed with the unprocessed form of PS1, which has higher affinity for plakoglobin and β-catenin than processed PS1. These results provide a new explanation for the effects of PS1 on gene transcription mediated by β-catenin in epithelial cells. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)1401-1411
JournalJournal of Biological Chemistry
Volume281
DOIs
Publication statusPublished - 20 Jan 2006

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