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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1011

Taylor, R C; Brumatti, G; Ito, S; Hengartner, M O; Derry, W B; Martin, S J (2007). Establishing a blueprint for CED-3-dependent killing through identification of multiple substrates for this protease. Journal of Biological Chemistry, 282(20):15011-15021.

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Abstract

Genetic studies have established that the cysteine protease CED-3 plays a central role in coordinating programmed cell death in Caenorhabditis elegans. However, it remains unclear how CED-3 activation results in cell death because few substrates for this protease have been described. We have used a global proteomics approach to seek substrates for CED-3 and have identified 22 worm proteins that undergo CED-3-dependent proteolysis. Proteins that were found to be substrates for CED-3 included the cytoskeleton proteins actin, myosin light chain, and tubulin, as well as proteins involved in ATP synthesis, cellular metabolism, and chaperone function. We estimate that approximately 3% of the C. elegans proteome is susceptible to CED-3-dependent proteolysis. Notably, the endoplasmic reticulum chaperone calreticulin, which has been implicated in the recognition of apoptotic cells by phagocytes, was cleaved by CED-3 and was also cleaved by human caspases during apoptosis. Inhibitors of caspase activity blocked the appearance of calreticulin on the surface of apoptotic cells, suggesting a mechanism for the surface display of calreticulin during apoptosis. Further analysis of these substrates is likely to yield important insights into the mechanism of killing by CED-3 and its human caspase counterparts.

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:2007
Deposited On:11 Feb 2008 13:20
Last Modified:27 Nov 2013 23:00
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Taylor, R C; Brumatti, G; Ito, S; Hengartner, M O; Derry, W B; Martin, S J. Establishing a blueprint for CED-3-dependent killing through identification of multiple substrates for this protease. J. Biol. Chem. 2007, 282(20):15011-21. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M611051200
PubMed ID:17371877
Citations:Web of Science®. Times Cited: 23
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