IDENTIFICATION AND CLONING OF EI24, A GENE INDUCED BY P53 IN ETOPOSIDE-TREATED CELLS

To search for candidate genes involved in p53-mediated apoptosis, the differential display technique was used to identify RNA species whose expression was altered in murine NIH3T3 cells treated with the cytotox ic drug etoposide. We report here the isolation and characterization o f EI24, a novel gene whose 2.4 kb mRNA is induced following etoposide treatment. Induction of EI24 mRNA by etoposide required expression of wild-type p53 in murine embryonic fibroblasts which had been transform ed with the oncogenes E1A and T24 H-ras; and overexpression of functio nal p53 in these cells was sufficient to induce expression of the EI24 mRNA. The EI24 mRNA was also induced in a p53-dependent manner by ion izing irradiation of primary murine thymocytes. Isolation of a full-le ngth EI24 cDNA revealed that its protein product bears homology to CEL F37C12.2, a Caenorhabditis elegans protein of unknown function.