Journal Article

DZNE-2020-07615

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis.

Crawford, E. D. ; Seaman, J. E. ; Barber, A. E. ; David, D.DZNE* ; Babbitt, P. C. ; Burlingame, A. L. ; Wells, J. A. (Corresponding author)

2012
Macmillan London

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Please use a persistent id in citations: doi:10.1038/cdd.2012.99

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.

Keyword(s): Animals (MeSH) ; Apoptosis (MeSH) ; Caenorhabditis elegans: enzymology (MeSH) ; Caspases: metabolism (MeSH) ; Cell Line (MeSH) ; Drosophila: enzymology (MeSH) ; Humans (MeSH) ; Mass Spectrometry (MeSH) ; Mice (MeSH) ; Signal Transduction (MeSH) ; Substrate Specificity (MeSH) ; Caspases

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Contributing Institute(s):

1. Protein Aggregation and Aging (AG David)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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