Smurf1 restricts the antiviral function mediated by USP25 through promoting its ubiquitination and degradation.
Smurf1 restricts the antiviral function mediated by USP25 through promoting its ubiquitination and degradation.
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Smurfl 通过促进 USP25 泛素化和降解来限制 USP25 介导的抗病毒功能
DOI：
10.1016/j.bbrc.2018.03.015
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Lv Haitao
中科院分区：
文献类型：
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作者：
Qian Guanghui;Hu Xiaohan;Li Gen;Ding Yueyue;Zhu Liyan;Zheng Hui;Li Mei;Li Zhiheng;Pan Jian;Li Yiping;Li Gang;Yang Chun;Liu Ying;Xie Yi;Lv Haitao
蛋白质泛素化和去泛素化酶广泛参与先天免疫反应。泛素特异性蛋白酶25（USP 25）是一种去泛素化酶，已被证明在病毒感染和免疫中起重要作用。然而，USP 25如何被E3泛素连接酶降解和调节仍然知之甚少。在这里，我们确定了Smad泛素调节因子1（Smurf 1）作为USP 25的第一个新的E3泛素连接酶。Smurf 1过表达降低USP 25蛋白周转率，并且Smurf 1的E3连接酶酶活性是USP 25降解所必需的。此外，Smurf 1介导的USP 25降解是通过促进泛素蛋白酶体依赖性途径中USP 25的K48-连接多聚泛素化。重要的是，USP 25过表达限制水泡性口炎病毒（VSV）复制，并且USP 25对VSV复制的限制在Smurf 1稳定敲除细胞中增强。因此，我们的研究首次发现Smurf 1负调控USP 25介导的抗病毒功能。我们的研究结果揭示了Smurf 1在USP 25上的作用以及它们在VSV复制调控中的作用。
Protein ubiquitination and deubiquitination enzymes are widely involved in innate immune responses. The ubiquitin specific protease 25 (USP25), a deubiquitinating enzyme, has been demonstrated to play an important role in virus infection and immunity. However, how USP25 is degraded and regulated by E3 ubiquitin ligases remains poorly understood. Here, we identified Smad ubiquitin regulatory factor 1(Smurf1) as a first novel E3 ubiquitin ligase of USP25. Smurf1 overexpression decreases USP25 protein turnover, and the E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation. Additionally, Smurf1-mediated degradation of USP25 is via promoting the K48-linkage polyubiquitination of USP25 in an ubiquitin proteasome dependent pathway. Importantly, USP25 overexpression restricts vesicular stomatitis virus (VSV) replication and the restriction of VSV replication by USP25 is enhanced in Smurf1 stable knock down cells. Therefore, our study firstly identified that Smurf1 negatively regulated the antiviral function mediated by USP25. Our findings revealed a previously unrecognized role of Smurf1 acting on USP25 and also their roles in the regulation of VSV replications.