Global Mapping of the Topography and Magnitude of Proteolytic Events in Apoptosis
Melissa M. Dix*, Gabriel M. Simon*, Benjamin F. Cravatt†
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology
The Scripps Research Institute, 10550 N. Torrey Pines Rd. La Jolla, CA 92037
*These authors contributed equally to the work
†To whom correspondence should be addressed: cravatt@scripps.edu
SUMMARY: 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.
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This paper was published in Cell in the 22 August 2008 edition.