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EMBO Rep. 2016 Nov;17(11):1624-1640. Epub 2016 Oct 4.

Linear ubiquitination by LUBEL has a role in Drosophila heat stress response.

Author information

1
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
2
Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, London, UK.
3
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
4
Vienna Biocenter Core Facilities GmbH (VBCF), Vienna, Austria.
5
Humboldt-Universität zu Berlin IRI for the Life Sciences, Berlin, Germany.
6
Institute for Genetics, University of Cologne, Cologne, Germany.
7
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria fumiyo.ikeda@imba.oeaw.ac.at.

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.

KEYWORDS:

LUBEL ; deubiquitinase; linear chain; ubiquitin; ubiquitin E3 ligase

PMID:
27702987
PMCID:
PMC5090701
DOI:
10.15252/embr.201642378
[Indexed for MEDLINE]
Free PMC Article

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