PMID- 29733654
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20190613
IS  - 1535-3907 (Electronic)
IS  - 1535-3893 (Linking)
VI  - 17
IP  - 6
DP  - 2018 Jun 1
TI  - Identification of Immune-Responsive Gene 1 (IRG1) as a Target of A20.
PG  - 2182-2191
LID - 10.1021/acs.jproteome.8b00139 [doi]
AB  - A20 is a negative regulator of NF-kappaB signaling; it controls inflammatory 
      responses and ensures tissue homeostasis. A20 is thought to restrict NF-kappaB 
      activation both by its ubiquitin-editing activity as well as by its nonenzymatic 
      activities. Besides its role in NF-kappaB signaling, A20 also acts as a protective 
      factor inhibiting apoptosis and necroptosis. Because of the ability of A20 to 
      both ubiquitinate and deubiquitinate substrates, and its involvement in many 
      cellular processes, we hypothesized that deletion of A20 might generally impact 
      on protein levels, thereby disrupting cellular signaling. We performed a 
      differential proteomics study on bone marrow-derived macrophages (BMDMs) from 
      control and myeloid-specific A20 knockout mice, both in untreated conditions and 
      after LPS or TNF treatment, and demonstrated A20-dependent changes in protein 
      expression. Several inflammatory proteins were found up-regulated in the absence 
      of A20, even without an inflammatory stimulus, but, depending on the treatment 
      and the treatment time, more proteins were found regulated. Together these 
      protein changes may affect normal signaling events, which may disturb tissue 
      homeostasis and induce (autoimmune) inflammation, in agreement with A20s proposed 
      identity as a susceptibility gene for inflammatory disease. We further verify 
      that immune-responsive gene 1 (IRG1) is up-regulated in the absence of A20 and 
      that its levels are transcriptionally regulated.
FAU - Van Quickelberghe, Emmy
AU  - Van Quickelberghe E
AD  - VIB-UGent Center for Medical Biotechnology, B-9000 Ghent , Belgium.
FAU - Martens, Arne
AU  - Martens A
AD  - VIB-UGent Center for Inflammation Research, B-9052 Ghent , Belgium.
AD  - Department of Biomedical Molecular Biology , Ghent University , B-9052 Ghent , 
      Belgium.
FAU - Goeminne, Ludger J E
AU  - Goeminne LJE
AD  - VIB-UGent Center for Medical Biotechnology, B-9000 Ghent , Belgium.
FAU - Clement, Lieven
AU  - Clement L
FAU - van Loo, Geert
AU  - van Loo G
AD  - VIB-UGent Center for Inflammation Research, B-9052 Ghent , Belgium.
AD  - Department of Biomedical Molecular Biology , Ghent University , B-9052 Ghent , 
      Belgium.
FAU - Gevaert, Kris
AU  - Gevaert K
AUID- ORCID: 0000-0002-4237-0283
AD  - VIB-UGent Center for Medical Biotechnology, B-9000 Ghent , Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180511
PL  - United States
TA  - J Proteome Res
JT  - Journal of proteome research
JID - 101128775
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
RN  - EC 3.4.22.- (Tnfaip3 protein, mouse)
RN  - EC 4.2.1.- (Hydro-Lyases)
RN  - EC 4.2.1.79 (Irg1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/drug effects
MH  - Hydro-Lyases/antagonists & inhibitors/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Proteomics/*methods
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor alpha-Induced Protein 3/*deficiency/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
OTO - NOTNLM
OT  - A20
OT  - CAD
OT  - IRG1
OT  - TNFAIP3
OT  - bone marrow-derived macrophages
OT  - differential proteomics
EDAT- 2018/05/08 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/05/08 06:00
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/05/08 06:00 [entrez]
AID - 10.1021/acs.jproteome.8b00139 [doi]
PST - ppublish
SO  - J Proteome Res. 2018 Jun 1;17(6):2182-2191. doi: 10.1021/acs.jproteome.8b00139. 
      Epub 2018 May 11.