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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-12-7
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pubmed:abstractText |
Caspase-3 and -7 are considered functionally redundant proteases with similar proteolytic specificities. We performed a proteome-wide screen on a mouse macrophage lysate using the N-terminal combined fractional diagonal chromatography technology and identified 46 shared, three caspase-3-specific, and six caspase-7-specific cleavage sites. Further analysis of these cleavage sites and substitution mutation experiments revealed that for certain cleavage sites a lysine at the P5 position contributes to the discrimination between caspase-7 and -3 specificity. One of the caspase-7-specific substrates, the 40 S ribosomal protein S18, was studied in detail. The RPS18-derived P6-P5' undecapeptide retained complete specificity for caspase-7. The corresponding P6-P1 hexapeptide still displayed caspase-7 preference but lost strict specificity, suggesting that P' residues are additionally required for caspase-7-specific cleavage. Analysis of truncated peptide mutants revealed that in the case of RPS18 the P4-P1 residues constitute the core cleavage site but that P6, P5, P2', and P3' residues critically contribute to caspase-7 specificity. Interestingly, specific cleavage by caspase-7 relies on excluding recognition by caspase-3 and not on increasing binding for caspase-7.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1535-9484
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pubmed:author |
pubmed-author:DeceuninckAnneliesA,
pubmed-author:DeclercqWimW,
pubmed-author:DemonDieterD,
pubmed-author:GevaertKrisK,
pubmed-author:HelsensKennyK,
pubmed-author:ImpensFrancisF,
pubmed-author:MadderAnnemiekeA,
pubmed-author:RousseauFredericF,
pubmed-author:SchymkowitzJoostJ,
pubmed-author:Van DammePetraP,
pubmed-author:Van DurmeJoostJ,
pubmed-author:VandekerckhoveJoëlJ,
pubmed-author:Vanden BergheTomT,
pubmed-author:VandenabeelePeterP,
pubmed-author:VerspurtenJelleJ,
pubmed-author:WejdaMagdalenaM
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pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2700-14
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pubmed:dateRevised |
2011-3-3
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pubmed:meshHeading |
pubmed-meshheading:19759058-Amino Acid Sequence,
pubmed-meshheading:19759058-Amino Acids,
pubmed-meshheading:19759058-Animals,
pubmed-meshheading:19759058-Caspase 3,
pubmed-meshheading:19759058-Caspase 7,
pubmed-meshheading:19759058-Humans,
pubmed-meshheading:19759058-Mice,
pubmed-meshheading:19759058-Models, Molecular,
pubmed-meshheading:19759058-Molecular Sequence Data,
pubmed-meshheading:19759058-Peptides,
pubmed-meshheading:19759058-Plasmids,
pubmed-meshheading:19759058-Protein Processing, Post-Translational,
pubmed-meshheading:19759058-Proteome,
pubmed-meshheading:19759058-Reproducibility of Results,
pubmed-meshheading:19759058-Structure-Activity Relationship,
pubmed-meshheading:19759058-Substrate Specificity
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pubmed:year |
2009
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pubmed:articleTitle |
Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity.
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pubmed:affiliation |
Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB), Ghent 9052, Belgium.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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