dc.contributor.author | Ribeiro, PS | en_US |
dc.contributor.author | Kuranaga, E | en_US |
dc.contributor.author | Tenev, T | en_US |
dc.contributor.author | Leulier, F | en_US |
dc.contributor.author | Miura, M | en_US |
dc.contributor.author | Meier, P | en_US |
dc.date.accessioned | 2016-01-22T14:00:14Z | |
dc.date.issued | 2007-12-31 | en_US |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/10892 | |
dc.description.abstract | In 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.sponsorship | P.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.extent | 1467 - 1480 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | J Cell Biol | en_US |
dc.subject | Animals | en_US |
dc.subject | Apoptosis | en_US |
dc.subject | Caspases | en_US |
dc.subject | Catalytic Domain | en_US |
dc.subject | Cell Survival | en_US |
dc.subject | Drosophila Proteins | en_US |
dc.subject | Humans | en_US |
dc.subject | Inhibitor of Apoptosis Proteins | en_US |
dc.subject | Mice | en_US |
dc.subject | NIH 3T3 Cells | en_US |
dc.subject | Protein Binding | en_US |
dc.subject | RING Finger Domains | en_US |
dc.subject | Ubiquitination | en_US |
dc.subject | X-Rays | en_US |
dc.title | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells. | en_US |
dc.type | Article | |
dc.rights.holder | © 2007 The Rockefeller University Press. | |
dc.identifier.doi | 10.1083/jcb.200706027 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/18166655 | en_US |
pubs.issue | 7 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 179 | en_US |