Cooperation between p53-dependent and p53-independent apoptotic pathways in myeloid cells.

Apoptosis may involve p53-dependent and -independent pathways. Results presented here suggest a possible cooperation between these two types of pathways. M1/2 is a p53-nonproducer subclone that may undergo either a p53-independent apoptosis following growth factor deprivation or a p53-dependent apoptosis following reconstitution of wild-type p53 expression. The p53-independent apoptosis in these cells is a slow process occurring after a G0-G1 arrest. In contrast, the p53-dependent apoptosis is much more rapid and is characterized by early and late apoptotic phases, taking place in cell arrested at G0-G1 and S phase. The transition from early to late apoptosis correlated with the levels of the p53 protein. Concomitant induction of both apoptotic pathways accelerated cell death and facilitated the transition from early to late apoptotic phase. The interaction between these pathways is further supported by the finding that mutant p53 interferes with p53-independent apoptosis. Thus, although apoptosis can occur via either p53-dependent or -independent pathways, under certain conditions the two pathways may interact with each other.