|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2005-5-3
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Notch1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1534-5807
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
8
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
665-76
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:15866158-Alopecia,
pubmed-meshheading:15866158-Animals,
pubmed-meshheading:15866158-Calcineurin,
pubmed-meshheading:15866158-Cell Cycle Proteins,
pubmed-meshheading:15866158-Cell Differentiation,
pubmed-meshheading:15866158-Cell Division,
pubmed-meshheading:15866158-Cells, Cultured,
pubmed-meshheading:15866158-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15866158-DNA-Binding Proteins,
pubmed-meshheading:15866158-Down-Regulation,
pubmed-meshheading:15866158-Gene Expression Regulation, Developmental,
pubmed-meshheading:15866158-Keratinocytes,
pubmed-meshheading:15866158-Mice,
pubmed-meshheading:15866158-Mice, Knockout,
pubmed-meshheading:15866158-NFATC Transcription Factors,
pubmed-meshheading:15866158-Nuclear Proteins,
pubmed-meshheading:15866158-Phenotype,
pubmed-meshheading:15866158-Promoter Regions, Genetic,
pubmed-meshheading:15866158-Receptor, Notch1,
pubmed-meshheading:15866158-Receptors, Cell Surface,
pubmed-meshheading:15866158-Signal Transduction,
pubmed-meshheading:15866158-Transcription Factors
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control.
|
|
pubmed:affiliation |
Department of Biochemistry, Lausanne University, Epalinges, Switzerland.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
