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Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization
Abstract
A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by regulating the permeability of mitochondria. Mitochondria sequester several proteins that, if released, kill by activating caspases, the proteases that disassemble the cell. Cytokines activate caspases in a different way, by assembling receptor complexes that activate caspases directly; in this case, the subsequent mitochondrial permeabilization accelerates cell disassembly by amplifying caspase activity. We found that cytotoxic stress causes activation of caspase-2, and that this caspase is required for the permeabilization of mitochondria. Therefore, we argue that cytokine-induced and stress-induced apoptosis act through conceptually similar pathways in which mitochondria are amplifiers of caspase activity rather than initiators of caspase activation.
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Cited by
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738
Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy
Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312
DNA damage-induced cell death by apoptosis
Roos, W. P., & Kaina, B. (2006) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.07.007 · Cited by 1,500
Cell death by mitotic catastrophe: a molecular definition
Castedo, M., Perfettini, J.-L., Roumier, T., Andreau, K., Medema, R., & Kroemer, G. (2004) · Oncogene · doi:10.1038/sj.onc.1207528 · Cited by 1,269
Metadata
- Authors
- Lassus, P., Opitz-Araya, X., & Lazebnik, Y.
- Venue
- Science
- Published
- 2002-08-23
- Volume
- 297
- Issue
- 5585
- Pages
- 1352-1354
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1997879915
- Cited by
- 719
- References
- 0
- FWCI
- 33.26
- Type
- journal article
- Language
- en
- Open access
- closed
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- Lassus, P., Opitz-Araya, X., & Lazebnik, Y. (2002). Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization. Science. https://doi.org/10.1126/science.1074721
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