{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Meinander A"],"funding":["Breast Cancer Now","NIAID NIH HHS"],"pagination":["2770-83"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3380211"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(12)"],"pubmed_abstract":["Caspases have been extensively studied as critical initiators and executioners of cell death pathways. However, caspases also take part in non-apoptotic signalling events such as the regulation of innate immunity and activation of nuclear factor-?B (NF-?B). How caspases are activated under these conditions and process a selective set of substrates to allow NF-?B signalling without killing the cell remains largely unknown. Here, we show that stimulation of the Drosophila pattern recognition protein PGRP-LCx induces DIAP2-dependent polyubiquitylation of the initiator caspase DREDD. Signal-dependent ubiquitylation of DREDD is required for full processing of IMD, NF-?B/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-?B signalling via ubiquitin-mediated activation of DREDD. The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling."],"journal":["The EMBO journal"],"pubmed_title":["Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling."],"pmcid":["PMC3380211"],"funding_grant_id":["BREAST CANCER NOW RESEARCH CENTRE","U24 AI082663","AI60025","AI082663","R56 AI060025","R01 AI060025"],"pubmed_authors":["Meinander A","Tenev T","Runchel C","Ribeiro PS","Silverman N","Kim CH","Zvelebil M","Broemer M","Chen L","Meier P","Leulier F"],"additional_accession":[]},"is_claimable":false,"name":"Ubiquitylation of the initiator caspase DREDD is required for innate immune signalling.","description":"Caspases have been extensively studied as critical initiators and executioners of cell death pathways. However, caspases also take part in non-apoptotic signalling events such as the regulation of innate immunity and activation of nuclear factor-?B (NF-?B). How caspases are activated under these conditions and process a selective set of substrates to allow NF-?B signalling without killing the cell remains largely unknown. Here, we show that stimulation of the Drosophila pattern recognition protein PGRP-LCx induces DIAP2-dependent polyubiquitylation of the initiator caspase DREDD. Signal-dependent ubiquitylation of DREDD is required for full processing of IMD, NF-?B/Relish and expression of antimicrobial peptide genes in response to infection with Gram-negative bacteria. Our results identify a mechanism that positively controls NF-?B signalling via ubiquitin-mediated activation of DREDD. The direct involvement of ubiquitylation in caspase activation represents a novel mechanism for non-apoptotic caspase-mediated signalling.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jun","modification":"2020-11-22T08:36:43Z","creation":"2019-03-27T00:54:45Z"},"accession":"S-EPMC3380211","cross_references":{"pubmed":["22549468"],"doi":["10.1038/emboj.2012.121"]}}