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

I. Celardo, F. Grespi, A. Antonov, F. Bernassola, A. V. Garabadgiu, G. Melino, I. Amelio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere645
JournalCell Death and Disease
Volume4
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Bladder cancer
  • Breast cancer
  • Caspase-1
  • P63
  • Prostate cancer
  • Tumor suppression

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

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  • Cite this

    Celardo, I., Grespi, F., Antonov, A., Bernassola, F., Garabadgiu, A. V., Melino, G., & Amelio, I. (2013). Caspase-1 is a novel target of p63 in tumor suppression. Cell Death and Disease, 4(5), [e645]. https://doi.org/10.1038/cddis.2013.175