Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control.

Détails

ID Serval
serval:BIB_F0252EC8F515
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control.
Périodique
Developmental Cell
Auteur⸱e⸱s
Mammucari C., Tommasi di Vignano A., Sharov A.A., Neilson J., Havrda M.C., Roop D.R., Botchkarev V.A., Crabtree G.R., Dotto G.P.
ISSN
1534-5807 (Print)
ISSN-L
1534-5807
Statut éditorial
Publié
Date de publication
2005
Volume
8
Numéro
5
Pages
665-676
Langue
anglais
Résumé
The Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21(WAF1/Cip1) gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-Jkappa protein to the p21 promoter. We show here that Notch 1 activation functions also through a second Calcineurin-dependent mechanism acting on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene, Calcineurin contributes significantly to the transcriptional response of keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype, associated with altered expression of Notch-responsive genes involved in hair follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth/differentiation control.
Mots-clé
Alopecia/etiology, Animals, Calcineurin/antagonists &amp, inhibitors, Calcineurin/metabolism, Cell Cycle Proteins/genetics, Cell Differentiation, Cell Division, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p21, DNA-Binding Proteins/metabolism, Down-Regulation, Gene Expression Regulation, Developmental, Keratinocytes/cytology, Keratinocytes/metabolism, Mice, Mice, Knockout, NFATC Transcription Factors, Nuclear Proteins/metabolism, Phenotype, Promoter Regions, Genetic, Receptor, Notch1, Receptors, Cell Surface/metabolism, Signal Transduction, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:58
Dernière modification de la notice
20/08/2019 17:18
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