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

Tomoko Asaoka, Jorge Almagro, Christine Ehrhardt, Isabella Tsai, Alexander Schleiffer, Luiza Deszcz, Sini Junttila, Leonie Ringrose, Karl Mechtler, Anoop Kavirayani, Attila Gyenesei, Kay Hofmann, Peter Duchek, Katrin Rittinger, Fumiyo Ikeda

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12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1624-1640
Number of pages17
JournalEMBO Reports
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Asaoka, T., Almagro, J., Ehrhardt, C., Tsai, I., Schleiffer, A., Deszcz, L., Junttila, S., Ringrose, L., Mechtler, K., Kavirayani, A., Gyenesei, A., Hofmann, K., Duchek, P., Rittinger, K., & Ikeda, F. (2016). Linear ubiquitination by LUBEL has a role in Drosophila heat stress response. EMBO Reports, 17(11), 1624-1640. https://doi.org/10.15252/embr.201642378