Integration of Notch1 and calcineurin/NFAT signaling pathway in keratinocyte growth and differentiation control.
Publication date
2005Author
Mammukari, C.Tommasi di Vignano, A.
Sharov, A.A.
Neilson, J.
Havrda, M.C.
Roop, D.R.
Botchkarev, Vladimir A.
Crabtree, G.R.
Paolo Dotto, G
Keyword
DevelopmentRegulation(control)
Differentiation
Growth
Keratinocyte
Signal transduction
Calcineurin
Peer-Reviewed
YesOpen Access status
closedAccess
Metadata
Show full item recordAbstract
The Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J¿ 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.Version
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Mammukari, C., Tommasi di Vignano, A., Sharov, A. A., Neilson, J. and Botchkarev, V.A. et al. (2005). Integration of Notch1 and calcineurin/NFAT signaling pathway in keratinocyte growth and differentiation control. Developmental Cell. Vol. 8, No. 5, pp. 665-676.Link to Version of Record
https://doi.org/10.1016/j.devcel.2005.02.016Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.devcel.2005.02.016