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

摘要: p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The gene has different transcriptional start sites, generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)p63); addition alternative splicing at the 5′-end give rise to least five C-terminal isoforms. This complexity of structure probably fostered debate controversy on function cancer, TP63-harboring distinctive promoters, codifying for TAp63 ΔNp63 isoforms, having discrete functions. However, also drives expression target genes that have relevant role cancer metastasis. In this study, we identified novel target, caspase-1. Caspase-1 proinflammatory caspase, functions suppression. We show both promote caspase-1 by physical binding promoter. Consistent our vitro findings, direct correlation between human data sets. addition, survival estimation analysis demonstrated functional interaction represents predictor positive outcome cancers. Overall, report involved suppression, clinical underlines biological relevance finding suggests further clinically predictive biomarker.