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dc.contributor.authorBoucher, Davefr
dc.contributor.authorBlais, Véroniquefr
dc.contributor.authorDenault, Jean-Bernardfr
dc.date.accessioned2015-06-03T18:07:58Z
dc.date.available2015-06-03T18:07:58Z
dc.date.created2012fr
dc.date.issued2015-06-03
dc.identifierPMID: 22451931fr
dc.identifier.urihttp://hdl.handle.net/11143/6866
dc.description.abstractDuring apoptosis, hundreds of proteins are cleaved by caspases, most of them by the executioner caspase-3. However, caspase-7, which shares the same substrate primary sequence preference as caspase-3, is better at cleaving poly(ADP ribose) polymerase 1 (PARP) and Hsp90 cochaperone p23, despite a lower intrinsic activity. Here, we identified key lysine residues (K38KKK) within the N-terminal domain of caspase-7 as critical elements for the efficient proteolysis of these two substrates. Caspase-7’s N-terminal domain binds PARP and improves its cleavage by a chimeric caspase-3 by !30-fold. Cellular expression of caspase-7 lacking the critical lysine residues resulted in less-efficient PARP and p23 cleavage compared with cells expressing the wild-type peptidase. We further showed, using a series of caspase chimeras, the positioning of p23 on the enzyme providing us with a mechanistic insight into the binding of the exosite. In summary, we have uncovered a role for the N-terminal domain (NTD) and the N-terminal peptide of caspase-7 in promoting key substrate proteolysis.fr
dc.language.isoengfr
dc.relation.isformatofhttp://www.pnas.org/content/109/15/5669.longfr
dc.relation.ispartofISSN:0027-8424fr
dc.relation.ispartofProceedings of the National Academy of Sciences of the United Statesfr
dc.subjectAmino Acid Motifsfr
dc.subjectAmino Acid Sequencefr
dc.subjectApoptosisfr
dc.subjectCaspase 3/metabolismfr
dc.subjectCaspase 7/chemistry*fr
dc.subjectCaspase 7/metabolismfr
dc.subjectCell Linefr
dc.subjectHumansfr
dc.subjectIntramolecular Oxidoreductases/metabolism*fr
dc.subjectProtein Structure, Tertiaryfr
dc.subjectMolecular Sequence Datafr
dc.subjectModels, Molecularfr
dc.subjectPoly(ADP-ribose) Polymerases/metabolism*fr
dc.subjectProteolysis*fr
dc.subjectStrcuture-Activity Relationshipfr
dc.subjectSubstrate Specificityfr
dc.titleCaspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1 proteolysisfr
dc.typeArticlefr
dc.rights.holder© National Academy of Sciences 2015fr
udes.description.typestatusPost-publicationfr
udes.description.typepubRévisé et accepté par des pairsfr
udes.description.pages5669-5674fr
udes.description.period109(15)fr
udes.description.sponsorshipCanadian Institutes of Health Researchfr
udes.description.sponsorshipNatural Sciences and Engineering Research Councilfr
udes.description.diffusionDiffusé par Savoirs UdeS, le dépôt institutionnel de l'Université de Sherbrookefr
dc.identifier.bibliographicCitationBoucher et al. (2012). Caspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1 proteolysis. PNAS 109(15):5669-74.fr
udes.description.sourceProceedings of the National Academy of Sciences of the United Statesfr
udes.autorisation.depottruefr
udes.description.ordreauteursBoucher, Dave; Blais, Véronique; Denault, Jean-Bernard


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