USP2a negatively regulates IL-1-and virus-induced NF-B activation by deubiquitinating TRAF6
USP2a negatively regulates IL-1-and virus-induced NF-B activation by deubiquitinating TRAF6
复制标题
USP2a 通过去泛素化 TRAF6 负向调节 IL-1 和病毒诱导的 NF-B 激活
DOI：
10.1093/jmcb/mjs024
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发表时间：
2013-02-01
影响因子：
5.5
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
He, Xiao;Li, Yi;Shu, Hong-Bing
转录因子NF-B在许多生物学过程中起着关键作用，特别是免疫。NF-B活化的信号传导被巧妙地调节以避免有害的免疫效应。在这份报告中，我们确定了泛素特异性蛋白酶2亚型（USP 2a）作为一种新的负调节Toll样受体/IL-1和仙台病毒（SeV）诱导的NF-B激活。USP 2a的过表达抑制IL-1和SeV诱导的NF-B活化和炎性细胞因子的转录，而USP 2a的敲低或敲除具有相反的效果。USP 2a缺陷细胞在IL-1和SeV刺激下表现出增强的肿瘤坏死因子受体相关因子6（TRAF 6）泛素化。此外，USP 2a与TRAF 6组成性相关，并去除由IL-1和SeV刺激诱导的TRAF 6的K63连接的多聚泛素链。还鉴别了对其作用重要的USP 2a残基。由于TRAF 6在导致NF-B激活的多个途径中的重要性，这些发现为不同刺激触发的NF-B激活提供了一般调节机制。
The transcription factor NF-B plays critical roles in many biological processes, especially immunity. The signaling to NF-B activation is subtly regulated to avoid harmful immune effects. In this report, we identified ubiquitin-specific protease 2 isoform a (USP2a) as a novel negative regulator in Toll-like receptors/IL-1- and Sendai virus (SeV)-induced NF-B activation. Overexpression of USP2a inhibited IL-1- and SeV-induced NF-B activation and transcription of inflammatory cytokines, whereas the knockdown or knockout of USP2a had opposite effects. USP2a-deficient cells exhibited potentiated ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) upon stimulation by IL-1 and SeV. Furthermore, USP2a was constitutively associated with TRAF6, and removed K63-linked polyubiquitin chains of TRAF6 induced by IL-1 and SeV stimulation. The residues of USP2a important for their role were also identified. Because of the importance of TRAF6 in multiple pathways leading to NF-B activation, these findings provide a general regulatory mechanism for NF-B activation triggered by different stimuli.