Systematic name M14650
Brief description Genes down-regulated in primary keratinocytes by expression of constantly active NOTCH1 [GeneID=4851].
Full description or abstract Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16618808   Authors: Nguyen BC,Lefort K,Mandinova A,Antonini D,Devgan V,Della Gatta G,Koster MI,Zhang Z,Wang J,Tommasi di Vignano A,Kitajewski J,Chiorino G,Roop DR,Missero C,Dotto GP
Exact source Table 1S
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Source species Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
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Version history 3.0: Renamed from NGUYEN_KERATO_DN

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