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Science 23 August 2002:
Vol. 297. no. 5585, pp. 1352 - 1354
DOI: 10.1126/science.1074721
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Reports

Requirement for Caspase-2 in Stress-Induced Apoptosis Before Mitochondrial Permeabilization

Patrice Lassus, Ximena Opitz-Araya, Yuri Lazebnik*

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.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
*   To whom correspondence should be addressed. E-mail: lazebnik{at}cshl.org

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Components of the Cell Death Machine and Drug Sensitivity of the National Cancer Institute Cell Line Panel.
P. A. Svingen, D. Loegering, J. Rodriquez, X. W. Meng, P. W. Mesner Jr., S. Holbeck, A. Monks, S. Krajewski, D. A. Scudiero, E. A. Sausville, et al. (2004)
Clin. Cancer Res. 10, 6807-6820
   Abstract »    Full Text »    PDF »
A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.
S. Daniel, M. B. Arvelo, V. I. Patel, C. R. Longo, G. Shrikhande, T. Shukri, J. Mahiou, D. W. Sun, C. Mottley, S. T. Grey, et al. (2004)
Blood 104, 2376-2384
   Abstract »    Full Text »    PDF »
Migrate, Differentiate, Proliferate, or Die: Pleiotropic Functions of an Apical "Apoptotic Caspase".
S. Kumar (2004)
Sci. STKE 2004, pe49
   Abstract »    Full Text »    PDF »
Sequential Caspase-2 and Caspase-8 Activation Upstream of Mitochondria during Ceramideand Etoposide-induced Apoptosis.
C.-F. Lin, C.-L. Chen, W.-T. Chang, M.-S. Jan, L.-J. Hsu, R.-H. Wu, M.-J. Tang, W.-C. Chang, and Y.-S. Lin (2004)
J. Biol. Chem. 279, 40755-40761
   Abstract »    Full Text »    PDF »
Nuclear Localization of Apoptosis Protease Activating Factor-1 Predicts Survival after Tumor Resection in Early-Stage Non-Small Cell Lung Cancer.
B. Besse, C. Cande, J.-P. Spano, A. Martin, D. Khayat, T. Le Chevalier, T. Tursz, L. Sabatier, J.-C. Soria, and G. Kroemer (2004)
Clin. Cancer Res. 10, 5665-5669
   Abstract »    Full Text »    PDF »
Caspase-2 Can Function Upstream of Bid Cleavage in the TRAIL Apoptosis Pathway.
K. W. Wagner, I. H. Engels, and Q. L. Deveraux (2004)
J. Biol. Chem. 279, 35047-35052
   Abstract »    Full Text »    PDF »
BOK and NOXA Are Essential Mediators of p53-dependent Apoptosis.
A. G. Yakovlev, S. Di Giovanni, G. Wang, W. Liu, B. Stoica, and A. I. Faden (2004)
J. Biol. Chem. 279, 28367-28374
   Abstract »    Full Text »    PDF »
Requirement for Aspartate-cleaved Bid in Apoptosis Signaling by DNA-damaging Anti-cancer Regimens.
A. B. Werner, S. W. G. Tait, E. de Vries, E. Eldering, and J. Borst (2004)
J. Biol. Chem. 279, 28771-28780
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Proteolysis of the Mismatch Repair Protein MLH1 by Caspase-3 Promotes DNA Damage-induced Apoptosis.
F. Chen, O. K. Arseven, and V. L. Cryns (2004)
J. Biol. Chem. 279, 27542-27548
   Abstract »    Full Text »    PDF »
Bcl-2-regulated apoptosis and cytochrome c release can occur independently of both caspase-2 and caspase-9.
V. S. Marsden, P. G. Ekert, M. Van Delft, D. L. Vaux, J. M. Adams, and A. Strasser (2004)
J. Cell Biol. 165, 775-780
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Apaf-1 and caspase-9 accelerate apoptosis, but do not determine whether factor-deprived or drug-treated cells die.
P. G. Ekert, S. H. Read, J. Silke, V. S. Marsden, H. Kaufmann, C. J. Hawkins, R. Gerl, S. Kumar, and D. L. Vaux (2004)
J. Cell Biol. 165, 835-842
   Abstract »    Full Text »    PDF »
Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion.
J. Du and G. J. Hannon (2004)
PNAS 101, 8975-8980
   Abstract »    Full Text »    PDF »
Bid Truncation, Bid/Bax Targeting to the Mitochondria, and Caspase Activation Associated with Neutrophil Apoptosis Are Inhibited by Granulocyte Colony-Stimulating Factor.
N. A. Maianski, D. Roos, and T. W. Kuijpers (2004)
J. Immunol. 172, 7024-7030
   Abstract »    Full Text »    PDF »
Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes after simulated ischemia-reperfusion.
Y. Qin, T. L. Vanden Hoek, K. Wojcik, T. Anderson, C.-Q. Li, Z.-H. Shao, L. B. Becker, and K. J. Hamann (2004)
Am J Physiol Heart Circ Physiol 286, H2280-H2286
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Caspase-dependent Regulation of Histone Deacetylase 4 Nuclear-Cytoplasmic Shuttling Promotes Apoptosis.
G. Paroni, M. Mizzau, C. Henderson, G. Del Sal, C. Schneider, and C. Brancolini (2004)
Mol. Biol. Cell 15, 2804-2818
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The PIDDosome, a Protein Complex Implicated in Activation of Caspase-2 in Response to Genotoxic Stress.
A. Tinel and J. Tschopp (2004)
Science 304, 843-846
   Abstract »    Full Text »    PDF »
The NRIF3 Family of Transcriptional Coregulators Induces Rapid and Profound Apoptosis in Breast Cancer Cells.
D. Li, S. Das, T. Yamada, and H. H. Samuels (2004)
Mol. Cell. Biol. 24, 3838-3848
   Abstract »    Full Text »    PDF »
Nerve Growth Factor Withdrawal-mediated Apoptosis in Naive and Differentiated PC12 Cells through p53/Caspase-3-dependent and -independent Pathways.
H. Vaghefi, A. L. Hughes, and K. E. Neet (2004)
J. Biol. Chem. 279, 15604-15614
   Abstract »    Full Text »    PDF »


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