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Molecular and Cellular Biology, October 2004, p. 8649-8661, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8649-8661.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ß-Catenin-Dependent and -Independent Effects of N-Plakoglobin on Epidermal Growth and Differentiation

J. Teulière,¹ M. M. Faraldo,¹ M. Shtutman,² W. Birchmeier,³ J. Huelsken,⁴ J. P. Thiery,¹ and M. A. Glukhova^1*

UMR 144 CNRS-Institut Curie, Institut Curie, Section de Recherche, Paris, France,¹ Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel,² Max Delbrueck Center for Molecular Medicine, Berlin, Germany,³ Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland⁴

Received 4 February 2004/ Returned for modification 23 March 2004/ Accepted 9 July 2004

Both ß-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. ß-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (N122-PG) lacking the glycogen synthase kinase 3ß phosphorylation sites and therefore protected against degradation (transgenic line K5-N122-PG). The expression of N122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated ß-catenin. However, if expressed in ß-catenin-null epidermis, N122-PG did not induce new hair follicle germs and follicular tumors. Thus, N122-PG cannot substitute for ß-catenin in its signaling functions in vivo and the phenotype observed in K5-N122-PG mouse skin must be due to the aberrant activation of ß-catenin signaling. On the other hand, the expression of N122-PG in ß-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation.

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* Corresponding author. Mailing address: UMR 144 CNRS-Institut Curie, Institut Curie, Section de Recherche, 26 rue d'Ulm, 75248 Paris, Cedex 05, France. Phone: 33 1 42 34 6333. Fax: 33 1 42 34 6349. E-mail: Marina.Glukhova{at}curie.fr.

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Molecular and Cellular Biology, October 2004, p. 8649-8661, Vol. 24, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.19.8649-8661.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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