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Article
Nature 376, 37 - 43 (06 July 2002); doi:10.1038/376037a0

Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis

Donald W. Nicholson*, Ambereen Ali*, Nancy A. Thornberry, John P. Vaillancourt*, Connie K. Ding, Michel Gallant§, Yves Gareau§, Patrick R. Griffin, Marc Labelle§, Yuri A. Lazebnik, Neil A. Munday*, Sayyaparaju M. Raju, Mark E. Smulson, Ting-Ting Yamin, Violeta L. Yu* & Douglas K. Miller

Departments of * Biochemistry and Molecular Biology, and § Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Quebec, H9R 4P8 Canada
Departments of Biochemistry and Inflammation Research, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA
Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington DC, USA

The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (M r) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-lβ-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.

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