Premium
USP7‐TRIM27 axis negatively modulates antiviral type I IFN signaling
Author(s) -
Cai Juan,
Chen HongYan,
Peng ShuJie,
Meng JunLing,
Wang Yan,
Zhou Yu,
Qian XiaoPing,
Sun XiuYuan,
Pang XueWen,
Zhang Yu,
Zhang Jun
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700473rr
Subject(s) - ubiquitin , deubiquitinating enzyme , ubiquitin ligase , signal transduction , tank binding kinase 1 , microbiology and biotechnology , chemistry , gene knockdown , iκb kinase , biology , nf κb , biochemistry , apoptosis , gene , mitogen activated protein kinase kinase , protein kinase c
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‐β 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. FASEB J. 32, 5238–5249 (2018). www.fasebj.org