Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization

Lassus, Patrice, Opitz-Araya, Ximena, Lazebnik, Yuri (2002) Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science, 297 (5585). pp. 1352-1354. ISSN 1095-9203

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Apoptosis Apoptotic Protease-Activating Factor 1 Caspase 2 Caspases Cell Line, Transformed Cytochrome c Group DNA Damage Enzyme Activation Enzyme Repression Etoposide Humans Mitochondria Permeability Protein Transport Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Small Interfering RNA, Untranslated Signal Transduction Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha bcl-2-Associated X Protein
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > organelles, types and functions > mitochondria
organs, tissues, organelles, cell types and functions > organelles, types and functions
organs, tissues, organelles, cell types and functions
CSHL Authors:
Communities: CSHL labs > Labeznik lab
Depositing User: Matt Covey
Date: 2002
Date Deposited: 12 Dec 2012 17:29
Last Modified: 12 Dec 2012 17:29
Related URLs:
URI: https://repository.cshl.edu/id/eprint/26383

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