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The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation.
- Source :
-
Nature immunology [Nat Immunol] 2014 Mar; Vol. 15 (3), pp. 239-47. Date of Electronic Publication: 2014 Feb 02. - Publication Year :
- 2014
-
Abstract
- Here we found that the transcription repressor DREAM bound to the promoter of the gene encoding A20 to repress expression of this deubiquitinase that suppresses inflammatory NF-κB signaling. DREAM-deficient mice displayed persistent and unchecked A20 expression in response to endotoxin. DREAM functioned by transcriptionally repressing A20 through binding to downstream regulatory elements (DREs). In contrast, binding of the transcription factor USF1 to the DRE-associated E-box domain in the gene encoding A20 activated its expression in response to inflammatory stimuli. Our studies define the critical opposing functions of DREAM and USF1 in inhibiting and inducing A20 expression, respectively, and thereby the strength of NF-κB signaling. Targeting of DREAM to induce USF1-mediated A20 expression is therefore a potential anti-inflammatory strategy for the treatment of diseases associated with unconstrained NF-κB activity, such as acute lung injury.
- Subjects :
- Acute Lung Injury genetics
Acute Lung Injury metabolism
Animals
Chromatin Immunoprecipitation
Cysteine Endopeptidases
DNA-Binding Proteins genetics
Disease Models, Animal
Gene Expression Regulation immunology
Immunoblotting
Inflammation genetics
Intracellular Signaling Peptides and Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B genetics
NF-kappa B metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor alpha-Induced Protein 3
Ubiquitin-Protein Ligases genetics
DNA-Binding Proteins biosynthesis
Inflammation metabolism
Intracellular Signaling Peptides and Proteins biosynthesis
Kv Channel-Interacting Proteins metabolism
Repressor Proteins metabolism
Ubiquitin-Protein Ligases biosynthesis
Upstream Stimulatory Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 15
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24487321
- Full Text :
- https://doi.org/10.1038/ni.2823