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024 7 _ |a 10.1038/cdd.2012.99
|2 doi
024 7 _ |a pmid:22918439
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024 7 _ |a pmc:PMC3504717
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024 7 _ |a 1350-9047
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024 7 _ |a 1476-5403
|2 ISSN
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037 _ _ |a DZNE-2020-07615
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Crawford, E. D.
|0 P:(DE-HGF)0
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245 _ _ |a Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis.
260 _ _ |a London
|c 2012
|b Macmillan
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2012-08-24
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2012-12-01
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Caspases, 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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542 _ _ |i 2012-08-24
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|u http://www.springer.com/tdm
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650 _ 7 |a Caspases
|0 EC 3.4.22.-
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Apoptosis
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: enzymology
|2 MeSH
650 _ 2 |a Caspases: metabolism
|2 MeSH
650 _ 2 |a Cell Line
|2 MeSH
650 _ 2 |a Drosophila: enzymology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mass Spectrometry
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Substrate Specificity
|2 MeSH
700 1 _ |a Seaman, J. E.
|b 1
700 1 _ |a Barber, A. E.
|b 2
700 1 _ |a David, Della
|0 P:(DE-2719)2810353
|b 3
|u dzne
700 1 _ |a Babbitt, P. C.
|b 4
700 1 _ |a Burlingame, A. L.
|b 5
700 1 _ |a Wells, J. A.
|0 P:(DE-HGF)0
|b 6
|e Corresponding author
773 1 8 |a 10.1038/cdd.2012.99
|b : Springer Science and Business Media LLC, 2012-08-24
|n 12
|p 2040-2048
|3 journal-article
|2 Crossref
|t Cell Death & Differentiation
|v 19
|y 2012
|x 1350-9047
773 _ _ |a 10.1038/cdd.2012.99
|g Vol. 19, no. 12, p. 2040 - 2048
|0 PERI:(DE-600)1496681-5
|n 12
|q 19:12<2040 - 2048
|p 2040-2048
|t Cell death and differentiation
|v 19
|y 2012
|x 1350-9047
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504717
909 C O |o oai:pub.dzne.de:141293
|p VDB
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
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|6 P:(DE-2719)2810353
913 1 _ |a DE-HGF
|b Forschungsbereich Gesundheit
|l Erkrankungen des Nervensystems
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|0 G:(DE-HGF)POF3-342
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|v Disease Mechanisms and Model Systems
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914 1 _ |y 2012
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21