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

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 CPP3...

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Bibliographic Details
Published in:Nature (London) 1995-07, Vol.376 (6535), p.37-43
Main Authors: Nicholson, Donald W, Ali, Ambereen, Thornberry, Nancy A, Vaillancourt, John P, Ding, Connie K, Gallant, Michel, Gareau, Yves, Griffin, Patrick R, Labelle, Marc, Lazebnik, Yuri A, Munday, Neil A, Raju, Sayyaparaju M, Smulson, Mark E, Yamin, Ting-Ting, Yu, Violeta L, Miller, Douglas K
Format: Article
Language:English
Subjects:
Ageing, cell death
Amino Acid Sequence
Animals
Apoptosis - physiology
Biochemistry
Biological and medical sciences
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Caspase 1
Caspase 3
Caspases
Cell physiology
Cysteine Endopeptidases - chemistry
Cysteine Endopeptidases - isolation & purification
Cysteine Endopeptidases - metabolism
Cysteine Proteinase Inhibitors - pharmacology
Enzyme Precursors - metabolism
Fundamental and applied biological sciences. Psychology
Helminth Proteins - antagonists & inhibitors
Helminth Proteins - metabolism
Humanities and Social Sciences
Humans
Kinetics
Mass Spectrometry
Molecular and cellular biology
Molecular biology
Molecular Sequence Data
multidisciplinary
Poly(ADP-ribose) Polymerases - metabolism
Science
Science (multidisciplinary)
Tumor Cells, Cultured
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/376037a0