000141293 001__ 141293 000141293 005__ 20240324003348.0 000141293 0247_ $$2doi$$a10.1038/cdd.2012.99 000141293 0247_ $$2pmid$$apmid:22918439 000141293 0247_ $$2pmc$$apmc:PMC3504717 000141293 0247_ $$2ISSN$$a1350-9047 000141293 0247_ $$2ISSN$$a1476-5403 000141293 0247_ $$2altmetric$$aaltmetric:115351158 000141293 037__ $$aDZNE-2020-07615 000141293 041__ $$aEnglish 000141293 082__ $$a610 000141293 1001_ $$0P:(DE-HGF)0$$aCrawford, E. D.$$b0 000141293 245__ $$aConservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis. 000141293 260__ $$aLondon$$bMacmillan$$c2012 000141293 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2012-08-24 000141293 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2012-12-01 000141293 3367_ $$2DRIVER$$aarticle 000141293 3367_ $$2DataCite$$aOutput Types/Journal article 000141293 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1592319444_23892 000141293 3367_ $$2BibTeX$$aARTICLE 000141293 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000141293 3367_ $$00$$2EndNote$$aJournal Article 000141293 520__ $$aCaspases, cysteine proteases with aspartate specificity, are key players in programmed cell death across the metazoan lineage. Hundreds of apoptotic caspase substrates have been identified in human cells. Some have been extensively characterized, revealing key functional nodes for apoptosis signaling and important drug targets in cancer. But the functional significance of most cuts remains mysterious. We set out to better understand the importance of caspase cleavage specificity in apoptosis by asking which cleavage events are conserved across metazoan model species. Using N-terminal labeling followed by mass spectrometry, we identified 257 caspase cleavage sites in mouse, 130 in Drosophila, and 50 in Caenorhabditis elegans. The large majority of the caspase cut sites identified in mouse proteins were found conserved in human orthologs. However, while many of the same proteins targeted in the more distantly related species were cleaved in human orthologs, the exact sites were often different. Furthermore, similar functional pathways are targeted by caspases in all four species. Our data suggest a model for the evolution of apoptotic caspase specificity that highlights the hierarchical importance of functional pathways over specific proteins, and proteins over their specific cleavage site motifs. 000141293 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0 000141293 542__ $$2Crossref$$i2012-08-24$$uhttp://www.springer.com/tdm 000141293 588__ $$aDataset connected to CrossRef, PubMed, 000141293 650_7 $$0EC 3.4.22.-$$2NLM Chemicals$$aCaspases 000141293 650_2 $$2MeSH$$aAnimals 000141293 650_2 $$2MeSH$$aApoptosis 000141293 650_2 $$2MeSH$$aCaenorhabditis elegans: enzymology 000141293 650_2 $$2MeSH$$aCaspases: metabolism 000141293 650_2 $$2MeSH$$aCell Line 000141293 650_2 $$2MeSH$$aDrosophila: enzymology 000141293 650_2 $$2MeSH$$aHumans 000141293 650_2 $$2MeSH$$aMass Spectrometry 000141293 650_2 $$2MeSH$$aMice 000141293 650_2 $$2MeSH$$aSignal Transduction 000141293 650_2 $$2MeSH$$aSubstrate Specificity 000141293 7001_ $$aSeaman, J. E.$$b1 000141293 7001_ $$aBarber, A. E.$$b2 000141293 7001_ $$0P:(DE-2719)2810353$$aDavid, Della$$b3$$udzne 000141293 7001_ $$aBabbitt, P. C.$$b4 000141293 7001_ $$aBurlingame, A. L.$$b5 000141293 7001_ $$0P:(DE-HGF)0$$aWells, J. A.$$b6$$eCorresponding author 000141293 77318 $$2Crossref$$3journal-article$$a10.1038/cdd.2012.99$$b : Springer Science and Business Media LLC, 2012-08-24$$n12$$p2040-2048$$tCell Death & Differentiation$$v19$$x1350-9047$$y2012 000141293 773__ $$0PERI:(DE-600)1496681-5$$a10.1038/cdd.2012.99$$gVol. 19, no. 12, p. 2040 - 2048$$n12$$p2040-2048$$q19:12<2040 - 2048$$tCell death and differentiation$$v19$$x1350-9047$$y2012 000141293 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504717 000141293 909CO $$ooai:pub.dzne.de:141293$$pVDB 000141293 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810353$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE 000141293 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0 000141293 9141_ $$y2012 000141293 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCELL DEATH DIFFER : 2017 000141293 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000141293 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000141293 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000141293 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central 000141293 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000141293 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000141293 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000141293 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000141293 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000141293 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000141293 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - 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