M1-linked ubiquitination by LUBEL is required for inflammatory responses to oral infection in Drosophila

Cell Death and Differentiation
Anna L AaltoAnnika Meinander

Abstract

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 pepti...Continue Reading

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Citations

Jun 20, 2019·Journal of Cellular Physiology·Xiuling ShangRongguo Yu
Jan 29, 2020·Journal of Receptor and Signal Transduction Research·Peng LiQiuyun Tu
Jun 26, 2020·Journal of Receptor and Signal Transduction Research·David Mui, Ying Zhang
Dec 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Erin E McClure CarrollJoao H F Pedra
Oct 16, 2019·Journal of Cellular Physiology·Dezhi Huang, Yugang Jiang
Nov 23, 2019·Journal of Receptor and Signal Transduction Research·Guanqun Ma, Yingwu Liu
May 1, 2020·Journal of Inflammation·Gaohai ShaoZhao Yang
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Ting XinFang Hu
Oct 6, 2020·Journal of Receptor and Signal Transduction Research·Jianguo BinYunjun Xu
Jan 15, 2021·Cell Death and Differentiation·Akhee Sabiha JahanRune Busk Damgaard
Mar 12, 2021·Biochemical and Biophysical Research Communications·Banseok LeeKyoung Sang Cho
Mar 2, 2021·The FEBS Journal·Debdeep DuttaAshim Mukherjee
Jul 16, 2021·Cell Death and Differentiation·Christa KietzAnnika Meinander
Jul 10, 2021·Nature Chemical Biology·Yuanyuan YuMinglei Zhao

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Methods Mentioned

BETA
ubiquitination
transgenic
pull down
pulldown
immunoprecipitations
pulldowns
PCR
transfection
deubiquitination

Software Mentioned

Image J
Phyre2
PyMol
3i SlideBook6
NEMO
UCSF Chimera package

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