Proteomics

Dataset Information

44

Mouse WT vs. A20 KO BMDM differential proteomics


ABSTRACT: A20 is a negative regulator of NF-κB signaling, crucial to control inflammatory responses and ensure tissue homeostasis. A20 is thought to restrict NF-κB activation both by its ubiquitin-editing activity as by non-enzymatic activities. Besides its role in NF-κB 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 processes. We performed a differential proteomics study of bone marrow derived macrophages (BMDMs) from control and myeloid-specific A20 knockout mice, both in untreated conditions and after LPS and TNF treatment, and demonstrate proteome-wide changes in protein expression upon A20 deletion. Several inflammatory proteins are up-regulated in the absence of A20, even without an inflammatory stimulus. Depending on the treatment and the time, more proteins are regulated. Together these changes may affect multiple signaling pathways disturbing tissue homeostasis and inducing (autoimmune) inflammation, as suggested by genetic studies in patients.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus musculus  

TISSUE(S): Bone Marrow

DISEASE(S): Not Available

SUBMITTER: Emmy Van Quickelberghe  

LAB HEAD: Kris Gevaert

PROVIDER: PXD008726 | Pride | 2018-05-15

REPOSITORIES: Pride

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Publications

Identification of Immune-Responsive Gene 1 (IRG1) as a Target of A20.

Van Quickelberghe Emmy E   Martens Arne A   Goeminne Ludger J E LJE   Clement Lieven L   van Loo Geert G   Gevaert Kris K  

Journal of proteome research 20180511 6


A20 is a negative regulator of NF-κB signaling; it controls inflammatory responses and ensures tissue homeostasis. A20 is thought to restrict NF-κB activation both by its ubiquitin-editing activity as well as by its nonenzymatic activities. Besides its role in NF-κB 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 t  ...[more]

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