Oncogene-dependent apoptosis is mediated by caspase-9.
Understanding how oncogenic transformation sensitizes cells to apoptosis may provide a strategy to kill tumor cells selectively. We previously developed a cell-free system that recapitulates oncogene dependent apoptosis as reflected by activation of caspases, the core of the apoptotic machinery. Here, we show that this activation requires a previously identified apoptosis-promoting complex consisting of caspase-9, APAF-1, and cytochrome c. As predicted by the in vitro system, preventing caspase-9 activation blocked drug-induced apoptosis in cells sensitized by E1A, an adenoviral oncogene. Oncogenes, such as E1A, appear to facilitate caspase-9 activation by several mechanisms, including the control of cytochrome c release from the mitochondria.
Fearnhead
H O
HO
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Rodriguez
J
J
Govek
E E
EE
Guo
W
W
Kobayashi
R
R
Hannon
G
G
Lazebnik
Y A
YA
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
C506592:APAF1 protein, human; D017500:Adenovirus E1A Proteins; D053477:Apoptotic Protease-Activating Factor 1; D003574:Cytochrome c Group; D015513:Oncogene Proteins; D011506:Proteins; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases