| TAp63 and DeltaNp63 in cancer and epidermal development. | |
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MedLine Citation:
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PMID: 17264681 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 DeltaNp63, 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, DeltaNp63 protects from apoptosis by directly competing for TAp63 target promoters or sequestering it, forming inactive tetramers. Accordingly, p63 is expressed in epithelial tumors, 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 isoforms in epithelial development remains mostly unclear. Nevertheless, recent work utilizing in vivo genetic complementation of TAp63 and/or DeltaNp63 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. |
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Authors:
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Eleonora Candi; David Dinsdale; Alessandro Rufini; Paolo Salomoni; Richard A Knight; Martina Mueller; Peter H Krammer; Gerry Melino |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2007-02-03 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 6 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-15 Completed Date: 2007-07-16 Revised Date: 2012-02-24 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 274-85 Citation Subset: IM |
Affiliation:
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University of Rome Tor Vergata, Rome, Italy. candi@uniroma2.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals DNA-Binding Proteins / genetics*, physiology Epidermis / growth & development, metabolism* Humans Models, Biological Mutation Neoplasms / genetics*, pathology Protein Isoforms / genetics, physiology Trans-Activators / genetics*, physiology Transcription Factors Tumor Suppressor Proteins / genetics*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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GGP02251//Telethon |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Protein Isoforms; 0/TP63 protein, human; 0/Trans-Activators; 0/Transcription Factors; 0/Tumor Suppressor Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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