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 [10.1038/cddis.2013.175].

Caspase-1 is a novel target of p63 in tumor suppression

BERNASSOLA, FRANCESCA;MELINO, GENNARO;Amelio, I.
2013-01-01

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.
2013
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
RNA, Messenger; Promoter Regions, Genetic; Transcription Factors; Humans; HEK293 Cells; Caspase 1; Protein Binding; Transcriptional Activation; Protein Isoforms; Cell Line; Tumor Suppressor Proteins
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 [10.1038/cddis.2013.175].
Celardo, I; Grespi, F; Antonov, A; Bernassola, F; Garabadgiu, A; Melino, G; Amelio, I
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/102752
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 45
  • ???jsp.display-item.citation.isi??? 44
social impact