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dc.contributor.authorRibeiro, PSen_US
dc.contributor.authorKuranaga, Een_US
dc.contributor.authorTenev, Ten_US
dc.contributor.authorLeulier, Fen_US
dc.contributor.authorMiura, Men_US
dc.contributor.authorMeier, Pen_US
dc.date.accessioned2016-01-22T14:00:14Z
dc.date.issued2007-12-31en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/10892
dc.description.abstractIn addition to their well-known function in apoptosis, caspases are also important in several nonapoptotic processes. How caspase activity is restrained and shut down under such nonapoptotic conditions remains unknown. Here, we show that Drosophila melanogaster inhibitor of apoptosis protein 2 (DIAP2) controls the level of caspase activity in living cells. Animals that lack DIAP2 have higher levels of drICE activity. Although diap2-deficient cells remain viable, they are sensitized to apoptosis following treatment with sublethal doses of x-ray irradiation. We find that DIAP2 regulates the effector caspase drICE through a mechanism that resembles the one of the caspase inhibitor p35. As for p35, cleavage of DIAP2 is required for caspase inhibition. Our data suggest that DIAP2 forms a covalent adduct with the catalytic machinery of drICE. In addition, DIAP2 also requires a functional RING finger domain to block cell death and target drICE for ubiquitylation. Because DIAP2 efficiently interacts with drICE, our data suggest that DIAP2 controls drICE in its apoptotic and nonapoptotic roles.en_US
dc.description.sponsorshipP.S. Ribeiro is supported by a PhD fellowship (SFRH/BD/15219/2004) from the Fundação para a Ciência e Tecnologia and F. Leulier is supported by a Human Frontier Science Program fellowship (LT-0177/2004). E. Kuranaga and M. Miura are supported in part by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology (19109003, 17025010, 19040006, 19041026, and 19044013) and the Takeda Science Foundation.en_US
dc.format.extent1467 - 1480en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofJ Cell Biolen_US
dc.subjectAnimalsen_US
dc.subjectApoptosisen_US
dc.subjectCaspasesen_US
dc.subjectCatalytic Domainen_US
dc.subjectCell Survivalen_US
dc.subjectDrosophila Proteinsen_US
dc.subjectHumansen_US
dc.subjectInhibitor of Apoptosis Proteinsen_US
dc.subjectMiceen_US
dc.subjectNIH 3T3 Cellsen_US
dc.subjectProtein Bindingen_US
dc.subjectRING Finger Domainsen_US
dc.subjectUbiquitinationen_US
dc.subjectX-Raysen_US
dc.titleDIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells.en_US
dc.typeArticle
dc.rights.holder© 2007 The Rockefeller University Press.
dc.identifier.doi10.1083/jcb.200706027en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/18166655en_US
pubs.issue7en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume179en_US


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