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Spotlight on p63 (Guest Editors, Gerry Melino and Frank McKeon)
TAp63 and ΔNp63 in Cancer and Epidermal Development
Eleonora Candi, David Dinsdale, Allesandro Rufini, Paolo Salomoni, Richard A. Knight, Martina Mueller, Peter H. Krammer and Gerry Melino
volume 6 | issue 3
1 February 2007Pages: 274 - 284
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The epidermis is a multilayered stratified epithelium, continuously regenerated by differentiating keratinocytes, that requires the transcription factor p63 for its development and maintenance. The TP63 gene encodes two major protein isoforms, TAp63 and ΔNp63, which have both transactivating and transcriptional repressing activities and regulate a wide range of target genes. TAp63 shows clear pro-apoptotic activity, mediated both by death receptors (CD95, TNF, TRAIL) and mitochondrial (bax, puma) pathways. Conversely, ΔNp63 protects from apoptosis by directly competing for TAp63 target promoters or sequestering it, forming inactive tetramers. Accordingly, p63 is expressed in epithelial tumours, contributing to both tumorigenesis and chemoresistance. However, the predominant physiological role of p63 is in epithelial development, as demonstrated by the lack of epidermis and other epithelia in p63-deficient mice. The specific role of TAp63 and ΔNp63 isoforms in epithelial development remains mostly unclear. Nevertheless, recent work utilizing in vivo genetic complementation of TAp63 and/or ΔNp63 into a p63 null background has shed new light into the specific functions of the two isoforms and allowed the in vivo validation of several p63 transcriptional targets, originally identified by microarray analysis in in vitro systems. However, despite concerted efforts to address the role of p63 isoforms, several questions remain unanswered. The main aim of this review is to critically discuss the data available in the literature and thoroughly analyze the models proposed.
Authors
Eleonora Candi
University of Rome "Tor Vergata"; Rome, Italy
David Dinsdale
MRC Toxicology Unit, Leicester, United Kingdom
Allesandro Rufini
University of Rome "Tor Vergata"; Rome, Italy
Paolo Salomoni
MRC Toxicology Unit, Leicester, United Kingdom
Richard A. Knight
MRC Toxicology Unit, Leicester, United Kingdom
Martina Mueller
University Hospital; Heidelberg, Germany
Peter H. Krammer
University of Frankfurt, Frankfurt Germany
Gerry Melino
University of Rome
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.