Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3.

Mammalian caspases are a family of cysteine proteases that plays a critical role in apoptosis. We have analyzed caspase-2 processing in human cell lines containing defined mutations in caspase-3 and caspase-9. Here we demonstrate that caspase-2 processing, during cell death induced by UV irradiation, depends both on caspase-9 and caspase-3 ...
activity, while, during TNF-alpha-dependent apoptosis, capase-2 processing is independent of caspase-9 but still requires caspase-3. In vitro procaspase-2 is the preferred caspase cleaved by caspase-3, while caspase-7 cleaves procaspase-2 with reduced efficiency. We have also demonstrated that caspase-2-mediated apoptosis requires caspase-9 and that cells co-expressing caspase-2 and a dominant negative form of caspase-9 are impaired in activating a normal apoptotic response and release cytochrome c into the cytoplasm. Our findings suggest a role played by caspase-2 as a regulator of the mitochondrial integrity and open questions on the mechanisms responsible for its activation during cell death.
Mesh Terms:
Amino Acid Substitution, Animals, Apoptosis, Caspase 2, Caspase 3, Caspase 7, Caspase 9, Caspases, Cell Death, Cell Line, Female, Fibroblasts, Fluorescent Antibody Technique, Indirect, Gene Expression Regulation, Enzymologic, Gene Library, Humans, Mammals, Mutagenesis, Site-Directed, Recombinant Proteins, Transfection, Tumor Necrosis Factor-alpha, Ultraviolet Rays
J. Biol. Chem.
Date: Jun. 15, 2001
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