Fearnhead, H. O., Rodriguez, J., Govek, E. E., Guo, W., Kobayashi, R., Hannon, G., Lazebnik, Y. A. (1998) Oncogene-dependent apoptosis is mediated by caspase-9. Proc Natl Acad Sci U S A, 95 (23). pp. 13664-13669. ISSN 0027-8424
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Abstract
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.
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