1. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation
- Author
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Karine Lefort, Dennis R. Roop, Caterina Missero, G. Paolo Dotto, Maranke I. Koster, Dario Antonini, Anna Mandinova, Zhuo Zhang, Bach Cuc Nguyen, Giusy Della Gatta, Alice Tommasi di Vignano, Jan Kitajewski, Jian Wang, Vikram Devgan, Giovanna Chiorino, Nguyen, Bc, Lefort, K, Mandinova, A, Antonini, Dario, Devgan, V, Della Gatta, G, Koster, Mi, Zhang, Z, Wang, J, Tommasi di Vignano, A, Kitajewski, J, Chiorino, G, Roop, Dr, Missero, Caterina, and Dotto, Gp
- Subjects
Keratinocytes ,Cellular differentiation ,Notch signaling pathway ,Biology ,Cell fate determination ,DNA-binding protein ,Mice ,Genetics ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Receptor, Notch1 ,Promoter Regions, Genetic ,Transcription factor ,DNA Primers ,Base Sequence ,Tumor Suppressor Proteins ,Cell Differentiation ,Cell cycle ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Trans-Activators ,IRF7 ,sense organs ,Keratinocyte ,Developmental Biology ,Research Paper ,Transcription Factors - 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.
- Published
- 2006