CELL-TYPE-SPECIFIC INHIBITION OF P53-MEDIATED APOPTOSIS BY MDM2

The effect of excess mdm2 on p53-mediated apoptosis was investigated i n two human-derived cell lines, H1299 and HeLa. In H1299 cells, overex pression of mdm2 resulted in effective protection from apoptosis. This protective effect was seen only under conditions allowing the formati on of p53-Mdm2 complexes. In contrast, excess mdm2 failed to abolish p 53-mediated apoptosis in HeLa cells, despite a complete abrogation of p53-dependent sequence-specific transcriptional activation (SST). Thes e data strongly support the contention that SST is dispensable for at least some types of p53-mediated apoptosis. Further, they suggest that one of the roles of mdm2 may be to modulate the apoptotic activity of p53, in a manner which is dictated by the pathway through which p53 i nduces apoptosis in a given cell type.