The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
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DOI：
10.1038/ni1110
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发表时间：
2004-10-01
影响因子：
30.5
通讯作者：
Ma, A
中科院分区：
文献类型：
--
作者：
Boone, DL;Turer, EE;Ma, A
A20是终止肿瘤坏死因子（TNF）诱导的信号所需的胞质蛋白。我们在这里表明，小鼠在A20和TNF或A20和TNF受体1的双重缺陷发展自发性炎症，表明A20也是至关重要的调节TNF-独立的信号在体内。A20是终止Toll样受体诱导的转录因子NF-κ B活性和巨噬细胞中促炎基因表达所必需的，这种功能保护小鼠免受内毒素休克。A20通过从信号分子TRAF 6直接去除泛素部分来生物化学地实现这一点。这种去泛素化酶在限制TLR信号中的关键功能强调了在先天免疫细胞中调节泛素缀合的重要性。
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.