Mechanisms of p53-induced apoptosis: in search of genes which are regulated during p53-mediated cell death

The tumor suppressor gene p53 is a major player in the protection of cells from DNA damage. In the majority of human cancers, p53 is functionally inac tivated - mostly by mutations but also by interaction with viral or cellula r proteins. Wild-type p53 is involved in essential functions such as DNA re pair, transcription, genomic stability, senescence, cell cycle control and apoptosis. It was shown to be a sequence-specific transcriptional activator , and this activity appears to be necessary to impose growth arrest. A majo r target gene which participates in p53-mediated growth arrest is p21/Waf1, an inhibitor of cyclin-dependent kinases. Whether or not transcriptional a ctivation of target genes is required for p53-mediated apoptosis may depend on the cell type and external factors, and the mechanism of cell death ind uction is not clear yet. We have employed clones of the M1 myeloid leukemic cell line expressing a temperature-sensitive p53 mutant to study genes whi ch are regulated during p53-induced apoptosis. (C) 1998 Elsevier Science Ir eland Ltd. All rights reserved.