PMID- 33932090
OWN - NLM
STAT- MEDLINE
DCOM- 20211112
LR  - 20211116
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 288
IP  - 20
DP  - 2021 Oct
TI  - HOIL-1-catalysed, ester-linked ubiquitylation restricts IL-18 signaling in 
      cytotoxic T cells but promotes TLR signalling in macrophages.
PG  - 5909-5924
LID - 10.1111/febs.15896 [doi]
AB  - The atypical E3 ligase HOIL-1 forms ester bonds between ubiquitin and 
      serine/threonine residues in proteins, but the physiological roles of this 
      unusual modification are unknown. We now report that IL-18 signalling leading to 
      the production of interferon gamma (IFNgamma) and granulocyte-macrophage 
      colony-stimulating factor (GM-CSF) is enhanced in cytotoxic T cells from knock-in 
      mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant, demonstrating that 
      the formation of HOIL-1-catalysed ester-linked ubiquitin bonds restricts the 
      activation of this pathway. We show that the interaction of IRAK2 with TRAF6 is 
      required for IL-18-stimulated IFN-gamma and GM-CSF production, and that the increased 
      production of these cytokines in cytotoxic T cells from HOIL-1[C458S] mice 
      correlates with an increase in both the number and size of the Lys63/Met1-linked 
      hybrid ubiquitin chains attached to IRAK2 in these cells. In contrast, the 
      secretion of IL-12 and IL-6 and the formation of il-12 and il-6 mRNA induced in 
      bone marrow-derived macrophages (BMDMs) by prolonged stimulation with 
      TLR-activating ligands that signal via myddosomes, which also requires the 
      interaction of IRAK2 with TRAF6, were not increased but modestly reduced in 
      HOIL-1[C458S] BMDM. The decreased production of these cytokines correlated with 
      reduced ubiquitylation of IRAK2. Our results establish that changes in 
      HOIL-1-catalysed ester-linked ubiquitylation can promote or reduce cytokine 
      production depending on the ligand, receptor and immune cell and may be explained 
      by differences in the ubiquitylation of IRAK2.
CI  - (c) 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf 
      of Federation of European Biochemical Societies.
FAU - Petrova, Tsvetana
AU  - Petrova T
AUID- ORCID: 0000-0003-2425-2459
AD  - MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, 
      University of Dundee, UK.
FAU - Zhang, Jiazhen
AU  - Zhang J
AD  - MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, 
      University of Dundee, UK.
FAU - Nanda, Sambit K
AU  - Nanda SK
AUID- ORCID: 0000-0003-2801-0967
AD  - MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, 
      University of Dundee, UK.
FAU - Figueras-Vadillo, Clara
AU  - Figueras-Vadillo C
AD  - MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, 
      University of Dundee, UK.
FAU - Cohen, Philip
AU  - Cohen P
AUID- ORCID: 0000-0001-7632-9492
AD  - MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life sciences, 
      University of Dundee, UK.
LA  - eng
GR  - MR/R021406/1/MRC_/Medical Research Council/United Kingdom
GR  - 209380/Z/17/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210506
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Esters)
RN  - 0 (Interleukin-18)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Ubiquitin)
RN  - EC 2.3.2.27 (Rbck1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
SB  - IM
CIN - FEBS J. 2021 Oct;288(20):5903-5908. PMID: 34322999
MH  - Animals
MH  - Esters/*chemistry
MH  - Interleukin-1 Receptor-Associated Kinases/metabolism
MH  - Interleukin-18/*metabolism
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Toll-Like Receptors/*metabolism
MH  - Ubiquitin/*chemistry
MH  - Ubiquitin-Protein Ligases/*physiology
MH  - *Ubiquitination
OTO - NOTNLM
OT  - HOIL-1
OT  - T cell
OT  - macrophage
OT  - myddosome
OT  - ubiquitylation
EDAT- 2021/05/02 06:00
MHDA- 2021/11/16 06:00
CRDT- 2021/05/01 08:41
PHST- 2021/03/19 00:00 [revised]
PHST- 2020/12/02 00:00 [received]
PHST- 2021/04/19 00:00 [accepted]
PHST- 2021/05/02 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/05/01 08:41 [entrez]
AID - 10.1111/febs.15896 [doi]
PST - ppublish
SO  - FEBS J. 2021 Oct;288(20):5909-5924. doi: 10.1111/febs.15896. Epub 2021 May 6.