| Literature DB >> 15866158 |
Cristina Mammucari1, Alice Tommasi di Vignano, Andrey A Sharov, Joel Neilson, Matthew C Havrda, Dennis R Roop, Vladimir A Botchkarev, Gerald R Crabtree, G Paolo Dotto.
Abstract
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.Entities:
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Year: 2005 PMID： 15866158 DOI： 10.1016/j.devcel.2005.02.016
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270