Overexpression of DRAM enhances p53‐dependent apoptosis

Tumor suppressor p53‐dependent apoptosis is thought to be one of the most important tumor‐suppressive mechanisms in human tumorigenesis. Till date, “super p53” mutants exhibiting more potent ability to induce apoptosis than wild‐type p53 have been reported. These super p53s may provide a clue for development of novel therapeutic targets. However, the major mechanism underlying the super p53‐dependent apoptosis remains unclear. To identify critical gene(s) in this mechanism, we performed a comprehensive and comparative expression analysis in p53‐null Saos ‐2 cells with conditional expression of wild‐type p53 and S121F, which was previously reported as a super p53 mutant. We identified damage‐regulated autophagy modulator ( DRAM ) as one of the genes that were more upregulated by S121F than wild‐type p53. Although knockdown of DRAM was not sufficient for reducing the ability of S121F to induce apoptosis, DRAM overexpression enhanced the ability in a wild‐type p53‐dependent manner. Here, we show that DRAM is an important gene for the enhancement of p53‐dependent apoptosis. Additional analysis of the mechanism of super p53‐dependent apoptosis may lead to the identification of novel drug targets for cancer therapy.