Oncogene-dependent apoptosis is mediated by caspase-9

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.

Item Type:	Paper
Uncontrolled Keywords:	Adenovirus E1A Proteins Apoptosis Apoptotic Protease-Activating Factor 1 Caspase 9 Caspases Cell Transformation, Neoplastic Cell Transformation, Viral Cells, Cultured Cytochrome c Group Enzyme Activation Fibroblasts Humans Oncogene Proteins Proteins
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
CSHL Authors:	Govek, Ellen Hannon, Gregory J. Lazebnik, Yuri Rodriquez, Joe
Communities:	CSHL labs > Hannon lab CSHL labs > Labeznik lab
Depositing User:	Matt Covey
Date:	1998
Date Deposited:	12 Dec 2012 17:30
Last Modified:	09 Nov 2017 17:21
PMCID:	PMC24876
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26398

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