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Title: Caspase-1 is a novel target of p63 in tumor suppression
Authors: Celardo, I.
Grespi, F.
Antonov, A.
Bernassola, F.
Garabadgiu, A. V.
Melino, G.
Amelio, I.
First Published: 23-May-2013
Publisher: Nature Publishing Group for Associazione Differenziamento e Morte Cellulare
Citation: Cell Death and Disease (2013) 4, e645
Abstract: p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The p63 gene has different transcriptional start sites, which generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)p63); in addition alternative splicing at the 5′-end give rise to at least five C-terminal isoforms. This complexity of gene structure has probably fostered the debate and controversy on p63 function in cancer, with TP63-harboring two distinctive promoters, codifying for the TAp63 and ΔNp63 isoforms, and having discrete functions. However, ΔNp63 also drives expression of target genes that have a relevant role in cancer and metastasis. In this study, we identified a novel p63 transcriptional target, caspase-1. Caspase-1 is proinflammatory caspase, which functions in tumor suppression. We show that both p63 isoforms promote caspase-1 expression by physical binding to its promoter. Consistent with our in vitro findings, we also identified a direct correlation between p63 and caspase-1 expression in human cancer data sets. In addition, survival estimation analysis demonstrated that functional interaction between p63 and caspase-1 represents a predictor of positive survival outcome in human cancers. Overall, our data report a novel p63 target gene involved in tumor suppression, and the clinical analysis underlines the biological relevance of this finding and suggests a further clinically predictive biomarker.
DOI Link: 10.1038/cddis.2013.175
ISSN: 2041-4889
eISSN: 2041-4889
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit
Appears in Collections:Published Articles, MRC Toxicology Unit

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