The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses - PubMed (original) (raw)
. 2004 Oct;5(10):1052-60.
doi: 10.1038/ni1110. Epub 2004 Aug 29.
Emre E Turer, Eric G Lee, Regina-Celeste Ahmad, Matthew T Wheeler, Colleen Tsui, Paula Hurley, Marcia Chien, Sophia Chai, Osamu Hitotsumatsu, Elizabeth McNally, Cecile Pickart, Averil Ma
Affiliations
- PMID: 15334086
- DOI: 10.1038/ni1110
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
David L Boone et al. Nat Immunol. 2004 Oct.
Erratum in
- Nat Immunol. 2005 Jan;6(1):114
Abstract
A20 is a cytoplasmic protein required for the termination of tumor necrosis factor (TNF)-induced signals. We show here that mice doubly deficient in either A20 and TNF or A20 and TNF receptor 1 developed spontaneous inflammation, indicating that A20 is also critical for the regulation of TNF-independent signals in vivo. A20 was required for the termination of Toll-like receptor-induced activity of the transcription factor NF-kappaB and proinflammatory gene expression in macrophages, and this function protected mice from endotoxic shock. A20 accomplished this biochemically by directly removing ubiquitin moieties from the signaling molecule TRAF6. The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells.
Comment in
- DUBbing down innate immunity.
Silverman N, Fitzgerald K. Silverman N, et al. Nat Immunol. 2004 Oct;5(10):1010-2. doi: 10.1038/ni1004-1010. Nat Immunol. 2004. PMID: 15454928 No abstract available.
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