140635 20240321220839.0 10.1038/s41418-018-0164-x doi pmid:30026495 pmid pmc:PMC6462001 pmc 1350-9047 ISSN 1476-5403 ISSN altmetric:45225269 altmetric DZNE-2020-06957 English 610 Aalto, Anna L 0 M1-linked ubiquitination by LUBEL is required for inflammatory responses to oral infection in Drosophila. London 2019 Macmillan online Crossref Springer Science and Business Media LLC 2018-07-19 print Crossref Springer Science and Business Media LLC 2019-05-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1588089481_27436 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Post-translational modifications such as ubiquitination play a key role in regulation of inflammatory nuclear factor-κB (NF-κB) signalling. The Drosophila IκB kinase γ (IKKγ) Kenny is a central regulator of the Drosophila Imd pathway responsible for activation of the NF-κB Relish. We found the Drosophila E3 ligase and HOIL-1L interacting protein (HOIP) orthologue linear ubiquitin E3 ligase (LUBEL) to catalyse formation of M1-linked linear ubiquitin (M1-Ub) chains in flies in a signal-dependent manner upon bacterial infection. Upon activation of the Imd pathway, LUBEL modifies Kenny with M1-Ub chains. Interestingly, the LUBEL-mediated M1-Ub chains seem to be targeted both directly to Kenny and to K63-linked ubiquitin chains conjugated to Kenny by DIAP2. This suggests that DIAP2 and LUBEL work together to promote Kenny-mediated activation of Relish. We found LUBEL-mediated M1-Ub chain formation to be required for flies to survive oral infection with Gram-negative bacteria, for activation of Relish-mediated expression of antimicrobial peptide genes and for pathogen clearance during oral infection. Interestingly, LUBEL is not required for mounting an immune response against systemic infection, as Relish-mediated antimicrobial peptide genes can be expressed in the absence of LUBEL during septic injury. Finally, transgenic induction of LUBEL-mediated M1-Ub drives expression of antimicrobial peptide genes and hyperplasia in the midgut in the absence of infection. This suggests that M1-Ub chains are important for Imd signalling and immune responses in the intestinal epithelia, and that enhanced M1-Ub chain formation is able to drive chronic intestinal inflammation in flies. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2018-07-19 Crossref https://creativecommons.org/licenses/by/4.0 Dataset connected to CrossRef, PubMed, Animals MeSH Bacterial Infections: genetics MeSH Bacterial Infections: microbiology MeSH Disease Models, Animal MeSH Drosophila: genetics MeSH Drosophila Proteins: genetics MeSH Gram-Negative Bacteria: pathogenicity MeSH Humans MeSH Immunity, Innate: genetics MeSH Inflammation: genetics MeSH Inflammation: microbiology MeSH Inhibitor of Apoptosis Proteins: genetics MeSH Mouth: microbiology MeSH Mouth: pathology MeSH NF-kappa B: genetics MeSH Protein Processing, Post-Translational: genetics MeSH RNA-Binding Proteins: genetics MeSH Signal Transduction: genetics MeSH Transcription Factors: genetics MeSH Ubiquitin: genetics MeSH Ubiquitin-Protein Ligases: genetics MeSH Ubiquitination: genetics MeSH Mohan, Aravind K 1 Schwintzer, Lukas P:(DE-2719)2810987 2 dzne Kupka, Sebastian 3 Kietz, Christa 4 Walczak, Henning 5 Broemer, Meike P:(DE-2719)2810307 6 dzne Meinander, Annika P:(DE-HGF)0 7 Corresponding author 10.1038/s41418-018-0164-x : Springer Science and Business Media LLC, 2018-07-19 5 860-876 journal-article Crossref Cell Death & Differentiation 26 2018 1350-9047 10.1038/s41418-018-0164-x Vol. 26, no. 5, p. 860 - 876 PERI:(DE-600)1496681-5 5 26:5<860 - 876 860-876 Cell death and differentiation 26 2018 1350-9047 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462001 oai:pub.dzne.de:140635 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2810987 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810307 DE-HGF Forschungsbereich Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3-300 Molecular Signaling 0 2019 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-30 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-30 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-30 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-30 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-30 JCR StatID:(DE-HGF)0100 StatID CELL DEATH DIFFER : 2021 2022-11-30 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-30 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-30 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-30 IF >= 10 StatID:(DE-HGF)9910 StatID CELL DEATH DIFFER : 2021 2022-11-30 I:(DE-2719)5000021 AG Brömer 1 Ubiquitin-mediated Processes in Neurodegenerative Diseases 0 journal VDB I:(DE-2719)5000021 UNRESTRICTED 10.1146/annurev.biochem.67.1.425 -- missing cx lookup -- Crossref 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