The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation.
Nat Immunol
; 15(3): 239-47, 2014 Mar.
Article
in En
| MEDLINE
| ID: mdl-24487321
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Ubiquitin-Protein Ligases
/
Intracellular Signaling Peptides and Proteins
/
DNA-Binding Proteins
/
Kv Channel-Interacting Proteins
/
Upstream Stimulatory Factors
/
Inflammation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2014
Type:
Article
Affiliation country:
United States