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J. Biol. Chem., Vol. 279, Issue 48, 49849-49856, November 26, 2004
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-Catenin and Plakoglobin N- and C-tails Determine Ligand Specificity*


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From the
Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra and the ||Unitat de Biologia Cel·lular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, E-08003 Barcelona, Spain
-Catenin and plakoglobin are related proteins involved in the regulation of adherens junctions and desmosomes. Moreover, by binding to Tcf-4, they can act as transcriptional modulators of genes involved in embryonic development and tumorigenesis. However, they associate to distinct Tcf-4 subdomains causing opposing effects on Tcf-4 binding to DNA: whereas
-catenin does not affect this binding, plakoglobin prevents it. Both proteins are composed by two N- and C-tails and a central armadillo repeat domain. Interaction of Tcf-4, as well as other desmosomal or adherens junction components, with
-catenin or plakoglobin takes place through the central armadillo domain. Here we show that, as reported for
-catenin, plakoglobin terminal tails also interact with the central domain and regulate the ability of this region to bind to different cofactors. Moreover the specificity of the interaction of
-catenin and plakoglobin with different subdomains in Tcf-4 or with other junctional components resides within the terminal tails and not in the armadillo domain. For instance, a chimeric protein in which the central domain of
-catenin was replaced by that of plakoglobin presented the same specificity as wild-type
-catenin. Therefore, the terminal tails of these proteins are responsible for discerning among binding of factors to the armadillo domain. These results contribute to the understanding of the molecular basis of the interactions established by these key regulators of epithelial tumorigenesis.
Received for publication, July 30, 2004 , and in revised form, September 17, 2004.
* This work was supported in part by Ministerio de Ciencia y Tecnología Grants BMC2003-00410 and SAF2003-02324 (to M. D. and A. G. H., respectively) and by Direcció General de Recerca Grants 2001SGR00410 and 2001SGR00197. 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.
The on-line version of this article (available at http://www.jbc.org) contains Supplemental Tables 13.
Recipient of a predoctoral fellowship awarded by Universitat Autónoma de Barcelona.
¶ Recipient of a predoctoral fellowship awarded by Ministerio de Educación y Ciencia.
** Recipient of a predoctoral fellowship awarded by Instituto de Salud Carlos III (Ministerio de Sanidad).

To whom correspondence may be addressed: Inst. Municipal d'Investigació Mèdica, c/Dr. Aiguader 80, E-08003 Barcelona, Spain. Tel.: 34-93-221-1009; Fax: 34-93-221-3237; E-mail: agarcia{at}imim.es. 
To whom correspondence maybe addressed: Unitat de Biofísica, Dept. Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. Tel.: 34-93-581-1870; Fax: 34-93-581-1907; E-mail: mireia.dunach{at}uab.es.
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