title: Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.
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.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA, and Department of Biochemistry, University of Lausanne, Switzerland.
authors.forename: Bach-Cuc
authors.initials: BC
authors.lastname: Nguyen
authors.forename: Karine
authors.initials: K
authors.lastname: Lefort
authors.forename: Anna
authors.initials: A
authors.lastname: Mandinova
authors.forename: Dario
authors.initials: D
authors.lastname: Antonini
authors.forename: Vikram
authors.initials: V
authors.lastname: Devgan
authors.forename: Giusy
authors.initials: G
authors.lastname: Della Gatta
authors.forename: Maranke I
authors.initials: MI
authors.lastname: Koster
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Alice
authors.initials: A
authors.lastname: Tommasi di Vignano
authors.forename: Jan
authors.initials: J
authors.lastname: Kitajewski
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Roop
authors.forename: Caterina
authors.initials: C
authors.lastname: Missero
authors.forename: G Paolo
authors.initials: GP
authors.lastname: Dotto
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins