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.
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 20 Jan 2006|
Raurell, I., Castaño, J., Francí, C., De Herreros, A. G., & Duñach, M. (2006). Presenilin-1 interacts with plakoglobin and enhances plakoglobin-Tcf-4 association: Implications for the regulation of β-catenin/Tcf-4-dependent transcription. Journal of Biological Chemistry, 281, 1401-1411. https://doi.org/10.1074/jbc.M508153200