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PMID: 18724940 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Global mapping of the topography and magnitude of proteolytic events in apoptosis.

Cell ·Vol. 134 ·No. 4 ·2008-08-22 ·Pages 679-91

Dix MM, Simon GM, Cravatt BF

Abstract

Proteolysis is a key regulatory process that promotes the (in)activation, translocation, and/or degradation of proteins. As such, there is considerable interest in methods to comprehensively characterize proteolytic pathways in biological systems. Here, we describe a robust and versatile proteomic platform that enables direct visualization of the topography and magnitude of proteolytic events on a global scale. We use this method to generate a proteome-wide map of proteolytic events induced by the intrinsic apoptotic pathway. This profile contained 91 characterized caspase substrates as well as 170 additional proteins not previously known to be cleaved during apoptosis. Surprisingly, the vast majority of proteolyzed proteins, regardless of the extent of cleavage, yielded persistent fragments that correspond to discrete protein domains, suggesting that the generation of active effector proteins may be a principal function of apoptotic proteolytic cascades.

MeSH Terms
Apoptosis Humans Jurkat Cells Mass Spectrometry Peptide Hydrolases/metabolism Proteins/metabolism Proteomics/methods
Chemicals
Proteins Peptide Hydrolases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dix Melissa M
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Simon Gabriel M
Cravatt Benjamin F
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.06.038
Published
2008-08-22
Pages
679-91
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2597167
Subset
IM
Grants
NCI NIH HHS · R01 CA087660 · United States
NCI NIH HHS · R01 CA087660-09 · United States
NCI NIH HHS · R37 CA087660 · United States
NCI NIH HHS · CA087660 · United States
Corrections
CommentIn
PMID: 18775303
External Links
PubMed source DOI: 10.1016/j.cell.2008.06.038 PMC Full Text View journal details
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