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.
Celardo, I., Grespi, F., Antonov, A., Bernassola, F., Garabadgiu, A., Melino, G., et al. (2013). Caspase-1 is a novel target of p63 in tumor suppression. CELL DEATH & DISEASE, 4, e645-e645.
|Tipologia:||Articolo su rivista|
|Citazione:||Celardo, I., Grespi, F., Antonov, A., Bernassola, F., Garabadgiu, A., Melino, G., et al. (2013). Caspase-1 is a novel target of p63 in tumor suppression. CELL DEATH & DISEASE, 4, e645-e645.|
|Settore Scientifico Disciplinare:||Settore BIO/11|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/cddis.2013.175|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2013|
|Titolo:||Caspase-1 is a novel target of p63 in tumor suppression|
|Autori:||Celardo, I; Grespi, F; Antonov, A; Bernassola, F; Garabadgiu, A; Melino, G; Amelio, I|
|Appare nelle tipologie:||01 - Articolo su rivista|