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Science 299 (5604): 214-215

Copyright © 2003 by the American Association for the Advancement of Science

Life and Death Decisions

Donald W. Nicholson and Nancy A. Thornberry

Screening small molecules for their ability to perturb a cellular pathway, a strategy called forward chemical genetics, can yield unexpected information about other pathway components. This is well illustrated by new work (Jiang et al.), as Nicholson and Thornberry discuss in their Perspective. Discovery of a small-molecule activator of apoptosis implicated a tumor suppressor protein and an oncoprotein in the regulation of the mitochondrial cell death pathway.

D. W. Nicholson is at the Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Montreal, Quebec HLH 3LI, Canada. N. A. Thornberry is at Merck Research Laboratories, Rahway, NJ 07065, USA. E-mail: nancy_thornberry{at}

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H. Vashistha, P. C. Singhal, A. Malhotra, M. Husain, P. Mathieson, M. A. Saleem, C. Kuriakose, S. Seshan, A. Wilk, L. DelValle, et al. (2012)
Am J Physiol Renal Physiol 303, F1629-F1640
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Death by Design: Where Curcumin Sensitizes Drug-resistant Tumours.
Anticancer Res 32, 2567-2584
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Prediction of protease substrates using sequence and structure features.
D. T. Barkan, D. R. Hostetter, S. Mahrus, U. Pieper, J. A. Wells, C. S. Craik, and A. Sali (2010)
Bioinformatics 26, 1714-1722
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Altered Expression of Regulators of Caspase Activity within Trophoblast of Normal Pregnancies and Pregnancies Complicated by Preeclampsia.
A. E. P. Heazell, H. R. Buttle, P. N. Baker, and I. P. Crocker (2008)
Reproductive Sciences 15, 1034-1043
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HAX-1 Represses Postmitochondrial Caspase-9 Activation and Cell Death During Hypoxia-Reoxygenation.
J. Shaw and L. A. Kirshenbaum (2006)
Circ. Res. 99, 336-338
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Autophagic programmed cell death by selective catalase degradation.
L. Yu, F. Wan, S. Dutta, S. Welsh, Z. Liu, E. Freundt, E. H. Baehrecke, and M. Lenardo (2006)
PNAS 103, 4952-4957
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Adi3 is a Pdk1-interacting AGC kinase that negatively regulates plant cell death.
T. P. Devarenne, S. K. Ekengren, K. F. Pedley, and G. B. Martin (2006)
EMBO J. 25, 255-265
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Prevention of Lymphocyte Apoptosis--A Potential Treatment of Sepsis?.
R. S. Hotchkiss, C. M. Coopersmith, and I. E. Karl (2005)
Clinical Infectious Diseases 41, S465-S469
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The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts.
V. Todorovicc, C.-C. Chen, N. Hay, and L. F. Lau (2005)
J. Cell Biol. 171, 559-568
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Antiapoptotic function of RNA-binding protein HuR effected through prothymosin {alpha}.
A. Lal, T. Kawai, X. Yang, K. Mazan-Mamczarz, and M. Gorospe (2005)
EMBO J. 24, 1852-1862
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Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8.
L. Yu, A. Alva, H. Su, P. Dutt, E. Freundt, S. Welsh, E. H. Baehrecke, and M. J. Lenardo (2004)
Science 304, 1500-1502
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The Selective Estrogen Receptor Modulator Arzoxifene and the Rexinoid LG100268 Cooperate to Promote Transforming Growth Factor {beta}-Dependent Apoptosis in Breast Cancer.
M. H. Rendi, N. Suh, W. W. Lamph, S. Krajewski, J. C. Reed, R. A. Heyman, A. Berchuck, K. Liby, R. Risingsong, D. B. Royce, et al. (2004)
Cancer Res. 64, 3566-3571
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A Cleaved Form of MAGE-A4 Binds to Miz-1 and Induces Apoptosis in Human Cells.
T. Sakurai, K. Itoh, H. Higashitsuji, T. Nagao, K. Nonoguchi, T. Chiba, and J. Fujita (2004)
J. Biol. Chem. 279, 15505-15514
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Apoptosis versus necrosis in acute pancreatitis.
M. Bhatia (2004)
Am J Physiol Gastrointest Liver Physiol 286, G189-G196
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Sustained Nitric Oxide Delivery Delays Nitric Oxide-Dependent Apoptosis in Macrophages: Contribution to the Physiological Function of Activated Macrophages.
S. Hortelano, P. G. Traves, M. Zeini, A. M. Alvarez, and L. Bosca (2003)
J. Immunol. 171, 6059-6064
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IGF-1 inhibits the mitochondrial apoptosis program in mesangial cells exposed to high glucose.
B. P. S. Kang, A. Urbonas, A. Baddoo, S. Baskin, A. Malhotra, and L. G. Meggs (2003)
Am J Physiol Renal Physiol 285, F1013-F1024
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Apoptosis - the p53 network.
S. Haupt, M. Berger, Z. Goldberg, and Y. Haupt (2003)
J. Cell Sci. 116, 4077-4085
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Nonradioactive Iodide Effectively Induces Apoptosis in Genetically Modified Lung Cancer Cells.
L. Zhang, S. Sharma, L. X. Zhu, T. Kogai, J. M. Hershman, G. A. Brent, S. M. Dubinett, and M. Huang (2003)
Cancer Res. 63, 5065-5072
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