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https://hdl.handle.net/2440/9361
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Type: | Journal article |
Title: | The biochemical mechanism of caspase-2 activation |
Author: | Baliga, B. Read, S. Kumar, S. |
Citation: | Cell Death and Differentiation, 2004; 11(11):1234-1241 |
Publisher: | Nature Publishing Group |
Issue Date: | 2004 |
ISSN: | 1350-9047 1476-5403 |
Statement of Responsibility: | B C Baliga, S H Read and S Kumar |
Abstract: | A unified model for initiator caspase activation has previously been proposed based on the biochemical analysis of caspase-8 and -9. Caspase-2 is structurally related to caspase-9, but its mechanism of activation is not known. Using an uncleavable mutant of caspase-2, we show that dimerization (and not processing) is the key event that drives initial procaspase-2 activation. Following dimerization, caspase-2 undergoes autocatalytic cleavage that promotes its stable dimerization and further enhances the catalytic activity of caspase-2. Although the caspase-2 zymogen does not require cleavage for the initial acquisition of activity, intersubunit cleavage is required to generate levels of activity required to induce cell death by overexpression. We also provide evidence that the reported disulfide bond linkage between two caspase-2 monomers is dispensable for caspase-2 dimerization. As caspase-2 does not require cleavage for its initial activation, our findings confirm caspase-2 to be a bona fide initiator caspase. |
Keywords: | Cell Line Animals Humans Disulfides Caspases Glutathione Transferase Recombinant Fusion Proteins Chromatography Electrophoresis, Polyacrylamide Gel Polymerase Chain Reaction Apoptosis Protein Biosynthesis Enzyme Activation Protein Structure, Tertiary Protein Binding Dimerization Mutation Catalysis Caspase 2 |
Description: | Copyright © 2004 Nature Publishing Group |
Provenance: | Published online 6 August 2004 |
DOI: | 10.1038/sj.cdd.4401492 |
Published version: | http://dx.doi.org/10.1038/sj.cdd.4401492 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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