Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition.
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.
Soengas
M S
MS
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Alarcón
R M
RM
Yoshida
H
H
Giaccia
A J
AJ
Hakem
R
R
Mak
T W
TW
Lowe
S W
SW
D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D011506:Proteins; D016159:Tumor Suppressor Protein p53; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases