title: Linear ubiquitination by LUBEL has a role in Drosophila heat stress response.
abstract: The HOIP ubiquitin E3 ligase generates linear ubiquitin chains by forming a complex with HOIL-1L and SHARPIN in mammals. Here, we provide the first evidence of linear ubiquitination induced by a HOIP orthologue in Drosophila We identify Drosophila CG11321, which we named Linear Ubiquitin E3 ligase (LUBEL), and find that it catalyzes linear ubiquitination in vitro We detect endogenous linear ubiquitin chain-derived peptides by mass spectrometry in Drosophila Schneider 2 cells and adult flies. Furthermore, using CRISPR/Cas9 technology, we establish linear ubiquitination-defective flies by mutating residues essential for the catalytic activity of LUBEL Linear ubiquitination signals accumulate upon heat shock in flies. Interestingly, flies with LUBEL mutations display reduced survival and climbing defects upon heat shock, which is also observed upon specific LUBEL depletion in muscle. Thus, LUBEL is involved in the heat response by controlling linear ubiquitination in flies.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Asaoka
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
authors.forename: Jorge
authors.initials: J
authors.lastname: Almagro
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Isabella
authors.initials: I
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.|Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors.forename: Alexander
authors.identifier: 0000-0001-6251-2747
authors.initials: A
authors.lastname: Schleiffer
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
authors.forename: Luiza
authors.initials: L
authors.lastname: Deszcz
authors.affiliation: Vienna Biocenter Core Facilities GmbH (VBCF), Vienna, Austria.
authors.forename: Sini
authors.initials: S
authors.lastname: Junttila
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.|Humboldt-Universität zu Berlin IRI for the Life Sciences, Berlin, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Ringrose
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.|Research Institute of Molecular Pathology (IMP), Vienna, Austria.
authors.forename: Karl
authors.identifier: 0000-0002-3392-9946
authors.initials: K
authors.lastname: Mechtler
authors.affiliation: Vienna Biocenter Core Facilities GmbH (VBCF), Vienna, Austria.
authors.forename: Anoop
authors.initials: A
authors.lastname: Kavirayani
authors.affiliation: Vienna Biocenter Core Facilities GmbH (VBCF), Vienna, Austria.
authors.forename: Attila
authors.initials: A
authors.lastname: Gyenesei
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany.
authors.forename: Kay
authors.identifier: 0000-0002-2289-9083
authors.initials: K
authors.lastname: Hofmann
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Duchek
authors.affiliation: Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Katrin
authors.identifier: 0000-0002-7698-4435
authors.initials: K
authors.lastname: Rittinger
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria fumiyo.ikeda@imba.oeaw.ac.at.
authors.forename: Fumiyo
authors.identifier: 0000-0003-0407-2768
authors.initials: F
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D002384:Catalysis; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D029721:Drosophila Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C533658:hoip protein, Drosophila; C425287:sharpin; D044767:Ubiquitin-Protein Ligases
keywords: 
  LUBEL
  ; deubiquitinase; linear chain; ubiquitin; ubiquitin E3 ligase