Caspase 10 levels are increased following DNA damage in a p53-dependent manner

p53 plays a central role in the cellular response to stressful stimuli, including DNA damage, aberrant growth signals, and hypoxia. Upon activation, it binds to a specific DNA binding motif and functions to transcriptionally activate or repress different groups of genes. The biologic outcome of these events can lead to cell-cycle arrest, DNA repair, or apoptosis. While many downstream targets of p53 have been identified, the factors that determine which of these outcomes will occur in an individual cell are less clear. In this study, we show that caspase 10, an initiator caspase, is induced in response to DNA damaging chemotherapeutic agents in a p53-dependent manner. Following treatment with etoposide or adriamycin, induction of caspase 10 occurred at both the mRNA and protein level. In contrast, DNA damage did not affect levels of caspase 8, another initiator caspase with significant structural and functional homology to caspase 10. By chromatin immunoprecipitation assay, p53 bound in vivo to multiple p...