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beta-catenin-dependent and -independent effects of deltaN-plakoglobin on epidermal growth and differentiation

Item Type:Article
Title:beta-catenin-dependent and -independent effects of deltaN-plakoglobin on epidermal growth and differentiation
Creators Name:Teuliere, J. and Faraldo, M.M. and Shtutman, M. and Birchmeier, W. and Huelsken, J. and Thiery, J.P. and Glukhova, M.A.
Abstract:Both {beta}-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. {beta}-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 ({delta}N122-PG) lacking the glycogen synthase kinase 3{beta} phosphorylation sites and therefore protected against degradation (transgenic line K5-{delta}N122-PG). The expression of {delta}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 {beta}-catenin. However, if expressed in {beta}-catenin-null epidermis, {delta}N122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for {beta}-catenin in its signaling functions in vivo and the phenotype observed in K5-{delta}N122-PG mouse skin must be due to the aberrant activation of {beta}-catenin signaling. On the other hand, the expression of {delta}N122-PG in {beta}-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.
Keywords:Beta Catenin, Cadherins, Cell Differentiation, Cysts, Cytoskeletal Proteins, Desmoplakins, Epidermis, Gamma Catenin, Proto-Oncogene Proteins c-myc, Reporter Genes, Transgenic Mice, Trans-Activators, Animals, Mice
Source:Molecular and Cellular Biology
ISSN:0270-7306
Publisher:American Society for Microbiology (U.S.A.)
Volume:24
Number:19
Page Range:8649-8661
Date:1 October 2004
Official Publication:https://doi.org/10.1128/MCB.24.19.8649-8661.2004
PubMed:View item in PubMed

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