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Originally published In Press as doi:10.1074/jbc.M508153200 on November 23, 2005

J. Biol. Chem., Vol. 281, Issue 3, 1401-1411, January 20, 2006
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Presenilin-1 Interacts with Plakoglobin and Enhances Plakoglobin-Tcf-4 Association

IMPLICATIONS FOR THE REGULATION OF beta-CATENIN/Tcf-4-DEPENDENT TRANSCRIPTION*

Imma Raurell{ddagger}1, Julio Castaño{ddagger}2, Clara Francí§, Antonio García de Herreros§3, and Mireia Duñach{ddagger}4

From the {ddagger}Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain and §Unitat de Biologia Cellular i Molecular, Institut Municipal d'InvestigacióMèdica, Universitat Pompeu Fabra, E-08003 Barcelona, Spain

Alzheimer disease-linked Presenilin-1 (PS1) is a negative modulator of beta-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 {gamma}-secretase activity and its interaction with beta-catenin. As presented in this report PS1 also binds plakoglobin with similar affinity as beta-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 beta-catenin than processed PS1. These results provide a new explanation for the effects of PS1 on gene transcription mediated by beta-catenin in epithelial cells.


Received for publication, July 26, 2005 , and in revised form, November 23, 2005.

* This work was supported in part by Fundació La Caixa Grant 01/045-00 (to A. G. H.) and by Spanish Ministry of Science and Technology Grants BMC2003-00410 (to M. D.) and SAF2003-0234 (to A. G. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Recipient of a postgraduate fellowship from the Instituto de Salud Carlos III.

2 Recipient of a postgraduate fellowship from the Ministry of Education.

3 To whom correspondence may be addressed. Tel.: 34-93-221-1009; Fax: 34-93-221-3237; E-mail: agarcia{at}imim.es. 4 To whom correspondence may be addressed. Tel.: 34-93-581-1870; Fax: 34-93-581-1907; E-mail: mireia.dunach{at}uab.es.


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