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Science 297 (5585): 1290-1291

Copyright © 2002 by the American Association for the Advancement of Science

A Cinderella Caspase Takes Center Stage

Sharad Kumar and David L. Vaux

It has been thought that permeabilization of mitochondria and release of cytochrome c is an ea rly event in apoptosis that is required for activation of caspases, the enzyme executioners of the apoptotic cascade. However, in a Perspective, Kumar and Vaux explain new findings (Lassus et al.) that implicate an often ignored caspase, caspase-2, in the early stages of apoptosis prior to mitochondrial permeabilization.

S. Kumar is at the Hanson Institute, Frome Road, Adelaide 5000, Australia. E-mail: sharad.kumar{at} D. L. Vaux is at the Walter and Eliza Hall Institute, Melbourne 3050, Australia.

Coenzyme Q10 Rescues Ethanol-induced Corneal Fibroblast Apoptosis through the Inhibition of Caspase-2 Activation.
C.-C. Chen, S.-W. Liou, C.-C. Chen, W.-C. Chen, F.-R. Hu, I.-J. Wang, and S.-J. Lin (2013)
J. Biol. Chem. 288, 11689-11704
   Abstract »    Full Text »    PDF »
Induction and Mechanism of Apoptosis by Hydroxycamptothecin in Human Tenon's Capsule Fibroblasts.
W. Tang, Y. Zhang, C. Qian, Z. Yuan, and J. Du (2012)
Invest. Ophthalmol. Vis. Sci. 53, 4874-4880
   Abstract »    Full Text »    PDF »
Otago Glaucoma Surgery Outcome Study: Electron Microscopy of Capsules around Molteno Implants.
A. G. Dempster, A. C. B. Molteno, T. H. Bevin, and A. M. Thompson (2011)
Invest. Ophthalmol. Vis. Sci. 52, 8300-8309
   Abstract »    Full Text »    PDF »
A tumor suppressor function for caspase-2.
L. H. Ho, R. Taylor, L. Dorstyn, D. Cakouros, P. Bouillet, and S. Kumar (2009)
PNAS 106, 5336-5341
   Abstract »    Full Text »    PDF »
The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats.
K. Niizuma, H. Endo, C. Nito, D. J. Myer, G. S. Kim, and P. H. Chan (2008)
PNAS 105, 16368-16373
   Abstract »    Full Text »    PDF »
Caspase-2: Vestigial Remnant or Master Regulator?.
C. M. Troy and E. M. Ribe (2008)
Science Signaling 1, pe42
   Abstract »    Full Text »    PDF »
GSK-3beta acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis.
C.-F. Lin, C.-L. Chen, C.-W. Chiang, M.-S. Jan, W.-C. Huang, and Y.-S. Lin (2007)
J. Cell Sci. 120, 2935-2943
   Abstract »    Full Text »    PDF »
An In vivo Tumor Model Exploiting Metabolic Response as a Biomarker for Targeted Drug Development.
C. Cullinane, D. S. Dorow, M. Kansara, N. Conus, D. Binns, R. J. Hicks, L. K. Ashman, G. A. McArthur, and D. M. Thomas (2005)
Cancer Res. 65, 9633-9636
   Abstract »    Full Text »    PDF »
Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells.
J.-C. Lee, C.-H. Lee, C.-L. Su, C.-W. Huang, H.-S. Liu, C.-N. Lin, and S.-J. Won (2005)
Carcinogenesis 26, 1716-1730
   Abstract »    Full Text »    PDF »
Bcl-2 Rescues Ceramide- and Etoposide-induced Mitochondrial Apoptosis through Blockage of Caspase-2 Activation.
C.-F. Lin, C.-L. Chen, W.-T. Chang, M.-S. Jan, L.-J. Hsu, R.-H. Wu, Y.-T. Fang, M.-J. Tang, W.-C. Chang, and Y.-S. Lin (2005)
J. Biol. Chem. 280, 23758-23765
   Abstract »    Full Text »    PDF »
Select forms of tumor cell apoptosis induce dendritic cell maturation.
S. Demaria, F. R. Santori, B. Ng, L. Liebes, S. C. Formenti, and S. Vukmanovic (2005)
J. Leukoc. Biol. 77, 361-368
   Abstract »    Full Text »    PDF »
Role of Omi/HtrA2 in Apoptotic Cell Death After Myocardial Ischemia and Reperfusion.
H.-R. Liu, E. Gao, A. Hu, L. Tao, Y. Qu, P. Most, W. J. Koch, T. A. Christopher, B. L. Lopez, E. S. Alnemri, et al. (2005)
Circulation 111, 90-96
   Abstract »    Full Text »    PDF »
Cinderology: the Cinderella of academic medicine.
L. Hazelton and C. Hickey (2004)
Can. Med. Assoc. J. 171, 1495-1496
   Full Text »    PDF »
Translocation of Bim to the Endoplasmic Reticulum (ER) Mediates ER Stress Signaling for Activation of Caspase-12 during ER Stress-induced Apoptosis.
N. Morishima, K. Nakanishi, K. Tsuchiya, T. Shibata, and E. Seiwa (2004)
J. Biol. Chem. 279, 50375-50381
   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 »
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 »
HOXA5-Induced Apoptosis in Breast Cancer Cells Is Mediated by Caspases 2 and 8.
H. Chen, S. Chung, and S. Sukumar (2004)
Mol. Cell. Biol. 24, 924-935
   Abstract »    Full Text »    PDF »
Mechanisms involved in methylmercuric chloride (MeHgCl)-induced suppression of human neutrophil apoptosis.
e. Moisan, e. Kouassi, and D. Girard (2003)
Human and Experimental Toxicology 22, 629-637
   Abstract »    PDF »
Insulin-Like Growth Factor-1 Receptor Activation Inhibits Oxidized LDL-Induced Cytochrome C Release and Apoptosis via the Phosphatidylinositol 3 Kinase/Akt Signaling Pathway.
Y. Li, Y. Higashi, H. Itabe, Y.-H. Song, J. Du, and P. Delafontaine (2003)
Arterioscler Thromb Vasc Biol 23, 2178-2184
   Abstract »    Full Text »    PDF »
Apoptosis is a major mechanism of deoxycholate-induced gastric mucosal cell death.
M. J. Redlak, M. S. Dennis, and T. A. Miller (2003)
Am J Physiol Gastrointest Liver Physiol 285, G870-G879
   Abstract »    Full Text »    PDF »
Crystal Structure of Caspase-2, Apical Initiator of the Intrinsic Apoptotic Pathway.
A. Schweizer, C. Briand, and M. G. Grutter (2003)
J. Biol. Chem. 278, 42441-42447
   Abstract »    Full Text »    PDF »
Novel Mechanisms of Apoptosis Induced by Histone Deacetylase Inhibitors.
M. J. Peart, K. M. Tainton, A. A. Ruefli, A. E. Dear, K. A. Sedelies, L. A. O'Reilly, N. J. Waterhouse, J. A. Trapani, and R. W. Johnstone (2003)
Cancer Res. 63, 4460-4471
   Abstract »    Full Text »    PDF »
Cell Stress-Associated Caspase Activation: Intrinsically Complex?.
E. M. Creagh and S. J. Martin (2003)
Sci. STKE 2003, pe11
   Abstract »    Full Text »    PDF »
Restoration of Fragile Histidine Triad (FHIT) Expression Induces Apoptosis and Suppresses Tumorigenicity in Breast Cancer Cell Lines.
C. Sevignani, G. A. Calin, R. Cesari, M. Sarti, H. Ishii, S. Yendamuri, A. Vecchione, F. Trapasso, and C. M. Croce (2003)
Cancer Res. 63, 1183-1187
   Abstract »    Full Text »    PDF »
Role of Prodomain in Importin-mediated Nuclear Localization and Activation of Caspase-2.
B. C. Baliga, P. A. Colussi, S. H. Read, M. M. Dias, D. A. Jans, and S. Kumar (2003)
J. Biol. Chem. 278, 4899-4905
   Abstract »    Full Text »    PDF »
A novel Apaf-1-independent putative caspase-2 activation complex.
S. H. Read, B. C. Baliga, P. G. Ekert, D. L. Vaux, and S. Kumar (2002)
J. Cell Biol. 159, 739-745
   Abstract »    Full Text »    PDF »

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