Rabbit Anti-Human TP63 Monoclonal Antibody, clone CQ7149

The BCL-2 family proteins are central regulators of apoptosis. However, cells deficient for BAX and BAK or overexpressing BCL-2 still succumb to oxidative stress upon DNA damage or matrix detachment. Here, we show that Delta Np63 alpha overexpression protects cells from oxidative stress induced by oxidants, DNA damage, anoikis, or ferroptosis-inducing agents. Conversely, Delta Np63 alpha deficiency increases oxidative stress. Mechanistically, Delta Np63 alpha orchestrates redox homeostasis through transcriptional control of glutathione biogenesis, utilization, and regeneration. Analysis of a lung squamous cell carcinoma dataset from The Cancer Genome Atlas (TCGA) reveals that TP63 amplification/ overexpression upregulates the glutathione metabolism pathway in primary human tumors. Strikingly, overexpression of Delta Np63 alpha promotes clonogenic survival of p53(-/-)Bax(-/-)Bak(-/-) cells against DNA damage. Furthermore, co-expression of BCL-2 and Delta Np63 alpha confers clonogenic survival against matrix detachment, disrupts the luminal clearance of mammary acini, and promotes cancer metastasis. Our findings highlight the need for a simultaneous blockade of apoptosis and oxidative stress to promote long-term cellular well-being.