Linear Ubiquitination by LUBEL Has a Role in Drosophila Heat Stress Response

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2016 Oct 6

PMID 27702987

Citations 20

Authors

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

Affiliations

Soon will be listed here.

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.

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