The ability of p53 to promote apoptosis in response to mitogenic oncogenes
appears to be critical for its tumor suppressor function, Caspase-9 and its
cofactor Apaf-1 were found to be essential downstream components of p53 in
Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells
deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to
apoptotic stimuli that mimic conditions in developing tumors. Inactivation
of Apaf-1 or caspase-9 substituted for p53 Loss in promoting the oncogenic
transformation of Myc-expressing cells. These results imply a role for Apaf
-1 and caspase-9 in controlling tumor development.