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@ARTICLE{Crawford:141293,
author = {Crawford, E. D. and Seaman, J. E. and Barber, A. E. and
David, Della and Babbitt, P. C. and Burlingame, A. L. and
Wells, J. A.},
title = {{C}onservation of caspase substrates across metazoans
suggests hierarchical importance of signaling pathways over
specific targets and cleavage site motifs in apoptosis.},
journal = {Cell death and differentiation},
volume = {19},
number = {12},
issn = {1350-9047},
address = {London},
publisher = {Macmillan},
reportid = {DZNE-2020-07615},
pages = {2040-2048},
year = {2012},
abstract = {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.},
keywords = {Animals / Apoptosis / Caenorhabditis elegans: enzymology /
Caspases: metabolism / Cell Line / Drosophila: enzymology /
Humans / Mass Spectrometry / Mice / Signal Transduction /
Substrate Specificity / Caspases (NLM Chemicals)},
cin = {AG David},
ddc = {610},
cid = {I:(DE-2719)1210004},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22918439},
pmc = {pmc:PMC3504717},
doi = {10.1038/cdd.2012.99},
url = {https://pub.dzne.de/record/141293},
}