UbcH8 regulates ubiquitin and ISG15 conjugation to RIG-I
UbcH8 regulates ubiquitin and ISG15 conjugation to RIG-I
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DOI：
10.1016/j.molimm.2007.07.021
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Shimotohno, Kunitada
中科院分区：
文献类型：
--
作者：
Arimoto, Kei-Ichiro;Konishi, Hideyuki;Shimotohno, Kunitada
RNA 解旋酶视黄酸诱导基因 I (RIG-I) 识别病毒双链 RNA 并启动信号级联，从而激活蛋白激酶 IKK alpha beta、TBK1 和 IKK epsilon，并随后激活转录因子 NF-kappa B 和 IRF3。我们最近报道 RIG-I 被泛素 E3 连接酶 RNF125 泛素化，导致蛋白酶体降解。据报道，RIG-I 被一种未鉴定的 ISG15（IFN 刺激基因，15 kDa）E3 连接酶 ISG 化。 UbcH8 是一种泛素 E2 结合酶，已被证明参与 RIG-I ISGylation。在这里，我们发现 UbcH8 通过 RNF125 抑制 RIG-I 泛素化，并且这种抑制通过 ISG15 的异位表达而缓解。或者，ISG15 与 RIG-I 的缀合被 RNF125 抑制。通过分析该调节回路，我们发现UbcH8和ISG15是RNF125 E3连接酶活性的功能调节因子，其调节RIG-I的泛素和ISG15缀合水平。 (c) 2007 Elsevier Ltd. 保留所有权利。
The RNA helicase retinoic inducible gene I (RIG-I) recognizes viral double-stranded RNA and initiates signaling cascades that lead to activation of the protein kinases IKK alpha beta, TBK1 and IKK epsilon, and to subsequent activation of the transcription factors NF-kappa B and IRF3. We recently reported that RIG-I was ubiquitinated by RNF125, an ubiquitin E3 ligase, leading to proteasomal degradation. RIG-I is also reported to be ISGylated by an unidentified ISG15 (IFN-stimulated gene, 15 kDa) E3 ligase. UbcH8, an ubiquitin E2 conjugating enzyme, was shown to be involved in RIG-I ISGylation. Here, we found that UbcH8 suppressed RIG-I ubiquitination by RNF125, and this suppression was relieved by ectopic expression of ISG15. Alternately, ISG15 conjugation to RIG-I was suppressed by RNF125. By analyzing this regulatory circuit, we found that UbcH8 and ISG15 are functional regulators of RNF125 E3 ligase activity, which regulates the level of ubiquitin and ISG15 conjugation of RIG-I. (c) 2007 Elsevier Ltd. All rights reserved.