NDLI: Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Masse, I. Barbollat-Boutrand, L. Molina, M. Berthier-Vergnes, O. Joly-Tonetti, N. Martin, M. T. Caron de Fromentel, C. Kanitakis, J. Lamartine, J.
Description	Country affiliation: France Author Affiliation: Masse I ( Centre de Génétique et de Physiologie Moléculaires et Cellulaires, CNRS UMR5534-Université Lyon I, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France. ingrid.masse@univ-lyon1.fr)
Abstract	The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that ΔNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by ΔNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by ΔNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to ΔNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between ΔNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2012.62
Journal	Cell Death and Disease
Volume Number	3
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-06-07
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, Non-u.s. Gov't Cell Proliferation Cytology Cells, Cultured Keratinocytes Epidermis Metabolism Membrane Proteins Discipline Cell Biology Tumor Suppressor Protein P53 Core Binding Factor Alpha 2 Subunit Down-regulation Genetics Cell Differentiation
Content Type	Text
Resource Type	Article

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