Please use this identifier to cite or link to this item:
https://doi.org/10.1126/sciadv.abc3465
DC Field | Value | |
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dc.title | Caspase-8-dependent gasdermin D cleavage promotes antimicrobial defense but confers susceptibility to TNF-induced lethality | |
dc.contributor.author | Demarco, B. | |
dc.contributor.author | Grayczyk, J.P. | |
dc.contributor.author | Bjanes, E. | |
dc.contributor.author | Roy, D.L. | |
dc.contributor.author | Tonnus, W. | |
dc.contributor.author | Assenmacher, C.-A. | |
dc.contributor.author | Radaelli, E. | |
dc.contributor.author | Fettrelet, T. | |
dc.contributor.author | Mack, V. | |
dc.contributor.author | Linkermann, A. | |
dc.contributor.author | Roger, T. | |
dc.contributor.author | Brodsky, I.E. | |
dc.contributor.author | Chen, K.W. | |
dc.contributor.author | Broz, P. | |
dc.date.accessioned | 2021-08-27T02:34:35Z | |
dc.date.available | 2021-08-27T02:34:35Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Demarco, B., Grayczyk, J.P., Bjanes, E., Roy, D.L., Tonnus, W., Assenmacher, C.-A., Radaelli, E., Fettrelet, T., Mack, V., Linkermann, A., Roger, T., Brodsky, I.E., Chen, K.W., Broz, P. (2020). Caspase-8-dependent gasdermin D cleavage promotes antimicrobial defense but confers susceptibility to TNF-induced lethality. Science Advances 6 (47) : eabc3465. ScholarBank@NUS Repository. https://doi.org/10.1126/sciadv.abc3465 | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/199675 | |
dc.description.abstract | Gasdermin D (GSDMD) is a pore-forming protein that promotes pyroptosis and release of proinflammatory cytokines. Recent studies revealed that apoptotic caspase-8 directly cleaves GSDMD to trigger pyroptosis. However, the molecular requirements for caspase-8-dependent GSDMD cleavage and the physiological impact of this signaling axis are unresolved. Here, we report that caspase-8-dependent GSDMD cleavage confers susceptibility to tumor necrosis factor (TNF)-induced lethality independently of caspase-1 and that GSDMD activation provides host defense against Yersinia infection. We further demonstrate that GSDMD inactivation by apoptotic caspases at aspartate 88 (D88) suppresses TNF-induced lethality but promotes anti-Yersinia defense. Last, we show that caspase-8 dimerization and autoprocessing are required for GSDMD cleavage, and provide evidence that the caspase-8 autoprocessing and activity on various complexes correlate with its ability to directly cleave GSDMD. These findings reveal GSDMD as a potential therapeutic target to reduce inflammation associated with mutations in the death receptor signaling machinery. Copyright c 2020 The Authors, some rights reserved;. | |
dc.publisher | American Association for the Advancement of Science | |
dc.rights | Attribution-NonCommercial 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | Scopus OA2020 | |
dc.type | Article | |
dc.contributor.department | MICROBIOLOGY AND IMMUNOLOGY | |
dc.description.doi | 10.1126/sciadv.abc3465 | |
dc.description.sourcetitle | Science Advances | |
dc.description.volume | 6 | |
dc.description.issue | 47 | |
dc.description.page | eabc3465 | |
Appears in Collections: | Elements Staff Publications |
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