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DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells
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 (DIAP...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373516/ https://www.ncbi.nlm.nih.gov/pubmed/18166655 http://dx.doi.org/10.1083/jcb.200706027 |
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author | Ribeiro, Paulo S. Kuranaga, Erina Tenev, Tencho Leulier, François Miura, Masayuki Meier, Pascal |
author_facet | Ribeiro, Paulo S. Kuranaga, Erina Tenev, Tencho Leulier, François Miura, Masayuki Meier, Pascal |
author_sort | Ribeiro, Paulo S. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2373516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-23735162008-06-30 DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells Ribeiro, Paulo S. Kuranaga, Erina Tenev, Tencho Leulier, François Miura, Masayuki Meier, Pascal J Cell Biol Research Articles 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. The Rockefeller University Press 2007-12-31 /pmc/articles/PMC2373516/ /pubmed/18166655 http://dx.doi.org/10.1083/jcb.200706027 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Ribeiro, Paulo S. Kuranaga, Erina Tenev, Tencho Leulier, François Miura, Masayuki Meier, Pascal DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title_full | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title_fullStr | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title_full_unstemmed | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title_short | DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells |
title_sort | diap2 functions as a mechanism-based regulator of drice that contributes to the caspase activity threshold in living cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373516/ https://www.ncbi.nlm.nih.gov/pubmed/18166655 http://dx.doi.org/10.1083/jcb.200706027 |
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