Comparative assessment of large-scale proteomic studies of apoptotic proteolysis.
Two proteomic methods were recently introduced to globally map proteolytic cleavage events in biological systems, one that characterized proteolyzed proteins by differential gel migration (PROTOMAP) and the other by enzymatic tagging and enrichment of the nascent N-terminal peptides generated by proteolysis (Subtiligase). Both technologies were applied to apoptosis, and each uncovered hundreds of novel proteolytic events. An initial survey, however, revealed only minimal overlap in the two data sets. In this article, we perform an in-depth comparative analysis of the PROTOMAP and Subtiligase results that assimilates the complementary information acquired by each method. This analysis uncovered substantial agreement between the PROTOMAP and Subtiligase data sets, which in integrated form yield a highly enriched portrait of the proteome-wide impact of proteolysis in apoptosis. We discuss the respective strengths of each proteomic method and the potential for these technologies to expand the scope and sensitivity of large-scale studies of proteolysis in biological systems.
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Gabriel M
GM
Simon
Melissa M
MM
Dix
Benjamin F
BF
Cravatt
D017209:Apoptosis; D030562:Databases, Protein; D013058:Mass Spectrometry; D010453:Peptide Synthases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013381:Subtilisins / Q000378:metabolism*
D010455:Peptides; D011506:Proteins; D013381:Subtilisins; D010453:Peptide Synthases; C117282:subtiligase