دورية أكاديمية
p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation
| العنوان: | p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation |
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| المؤلفون: | Chen, Yunfei, Wang, Lufan, Jin, Jiali, Luan, Yi, Chen, Cong, Li, Yu, Chu, Hongshang, Wang, Xinbo, Liao, Guanghong, Yu, Yue, Teng, Hongqi, Wang, Yanming, Pan, Weijuan, Fang, Lan, Liao, Lujian, Jiang, Zhengfan, Ge, Xin, Li, Bin, Wang, Ping |
| المساهمون: | Wang, P (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Cent Lab, Shanghai 200072, Peoples R China., Tongji Univ, Sch Life Sci & Technol, Dept Cent Lab, Shanghai 200072, Peoples R China., Tongji Univ, Shanghai Peoples Hosp 10, Dept Clin Lab Med, Shanghai 200072, Peoples R China., East China Normal Univ, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China., Peking Univ, Sch Life Sci, Minist Educ, State Key Lab Prot & Plant Gene Res,Key Lab Cell, Beijing 100000, Peoples R China., Peking Univ Tsinghua Univ Joint Ctr Life Sci, Beijing 100084, Peoples R China., Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, Shanghai Inst Immunol, Shanghai 200025, Peoples R China. |
| المصدر: | SCI |
| بيانات النشر: | JOURNAL OF EXPERIMENTAL MEDICINE |
| سنة النشر: | 2017 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | PROTEIN-KINASE, INTRACELLULAR DNA, INNATE IMMUNITY, DEUBIQUITINASE USP21, ANTIVIRAL RESPONSE, UBIQUITIN, REPLICATION, PATHWAY, SENSOR, CELL |
| الوصف: | Stimulator of IFN genes (STI N G) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STI N G function, how the ubiquitination/deubiquitination system is regulated by virus infection to control STI N G activity remains unknown. In this study, we found that USP21 is an important deubiquitinating enzyme for STI N G and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STI N G. HSV-1 infection recruited USP21 to STI N G at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STI N G-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses. ; National Key Research and Development Program of China [2016YFC0902102]; Ministry of Science and Technology of China (973 program) [2012CB910404]; National Natural Science Foundation of China [91519322, 91440104, 31501135]; Ministry of Education of China [20130076110022] ; SCI(E) ; ARTICLE ; 4 ; 991-1010 ; 214 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-1007 1540-9538 |
| العلاقة: | JOURNAL OF EXPERIMENTAL MEDICINE.2017,214(4),991-1010.; 1908794; http://hdl.handle.net/20.500.11897/474412Test; WOS:000398051100010 |
| DOI: | 10.1084/jem.20161387 |
| الإتاحة: | https://doi.org/20.500.11897/474412Test https://doi.org/10.1084/jem.20161387Test https://hdl.handle.net/20.500.11897/474412Test |
| رقم الانضمام: | edsbas.212FF31D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00221007 15409538 |
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| DOI: | 10.1084/jem.20161387 |