USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling
USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling
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USP7-TRIM27 轴负向调节抗病毒 I 型 IFN 信号传导。
DOI：
10.1096/fj.201700473rr
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发表时间：
2018-10-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
--
作者：
Cai, Juan;Chen, Hong-Yan;Zhang, Jun
泛素化和去泛素化是重要的翻译后调节机制，负责微调抗病毒信号。在这项研究中，我们确定了一个去泛素化酶，泛素特异性肽酶7/疱疹病毒相关的泛素特异性蛋白酶（USP 7/HAUSP）作为病毒诱导的信号传导的重要负调节剂。USP 7的过表达抑制仙台病毒和聚肌苷酸-聚胞苷酸和聚（脱氧腺苷酸-脱氧胸苷酸）诱导的ISRE和IFN-γ活化，并增强病毒复制。内源性USP 7表达的敲低或敲除具有相反的效果。免疫共沉淀试验表明，USP 7与三重基序（TRIM）27物理相互作用。这种相互作用在SeV感染后增强。此外，TNF受体相关因子家族成员相关NF-κ B结合激酶（TBK）-1在TRIM 27-USP 7复合物中被拉低。USP 7的过表达通过提高TRIM 27的稳定性促进TBK 1的泛素化和降解。内源性USP 7的敲除导致增强的TRIM 27降解和减少的TBK 1泛素化和降解，导致增强的I型IFN信号传导。我们的发现表明，USP 7通过稳定TRIM 27和促进TBK 1的降解而在抗病毒信号传导中充当负调节剂。陈洪-是的，彭，S.- J.，孟，J. - L.，王玉，Zhou，Y.，（1996年），中国科学院，钱学森P.，太阳，X。-是的，彭，X.- W.，张玉，Zhang，J. USP7-TRIM27 axis negatively modulates antivirus type I IFN signaling.
Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN- activation, and enhanced virus replication. Knockdown or knockout of endogenous USP7 expression had the opposite effect. Coimmunoprecipitation assays showed that USP7 physically interacted with tripartite motif (TRIM)27. This interaction was enhanced after SeV infection. In addition, TNF receptor-associated factor family member-associated NF-kappa-B-binding kinase (TBK)-1 was pulled down in the TRIM27-USP7 complex. Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27. Knockout of endogenous USP7 led to enhanced TRIM27 degradation and reduced TBK1 ubiquitination and degradation, resulting in enhanced type I IFN signaling. Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1.Cai, J., Chen, H.-Y., Peng, S.-J., Meng, J.-L., Wang, Y., Zhou, Y., Qian, X.-P., Sun, X.-Y., Pang, X.-W., Zhang, Y., Zhang, J. USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.