| First Author | Tiruppathi C | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 3 | Pages | 239-47 |
| PubMed ID | 24487321 | Mgi Jnum | J:209800 |
| Mgi Id | MGI:5568771 | Doi | 10.1038/ni.2823 |
| Citation | Tiruppathi C, et al. (2014) The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation. Nat Immunol 15(3):239-47 |
| abstractText | 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-kappaB 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-kappaB 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-kappaB activity, such as acute lung injury. |
