Inducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex.,PLoS Pathogens

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Inducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2019-08-12 , DOI: 10.1371/journal.ppat.1008002
Gang Xu ₁ , Zhangchuan Xia ₁ , Feiyan Deng ₁ , Lin Liu ₁ , Qiming Wang ₂ , Yi Yu ₃ , Fubing Wang ₄ , Chengliang Zhu ₅ , Weiyong Liu ₆ , Zhikui Cheng ₁ , Ying Zhu ₁ , Li Zhou ₇ , Yi Zhang ₈ , Mengji Lu ₉ , Shi Liu ₁

Affiliation

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan Province, China.
The Key Laboratory of Biosystems Homeostasis and Protection of the Ministry of Education and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Animal Biosafety Level III Laboratory at the Center for Animal Experiment, School of Medicine, Wuhan University, Wuhan, China.
Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Food and Pharmaceutical Engineering, Hubei University of Technology, Wuhan, China.
Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.

The galectin 3 binding protein (LGALS3BP, also known as 90K) is a ubiquitous multifunctional secreted glycoprotein originally identified in cancer progression. It remains unclear how 90K functions in innate immunity during viral infections. In this study, we found that viral infections resulted in elevated levels of 90K. Further studies demonstrated that 90K expression suppressed virus replication by inducing IFN and pro-inflammatory cytokine production. Upon investigating the mechanisms behind this event, we found that 90K functions as a scaffold/adaptor protein to interact with TRAF6, TRAF3, TAK1 and TBK1. Furthermore, 90K enhanced TRAF6 and TRAF3 ubiquitination and served as a specific ubiquitination substrate of TRAF6, leading to transcription factor NF-κB, IRF3 and IRF7 translocation from the cytoplasm to the nucleus. Conclusions: 90K is a virus-induced protein capable of binding with the TRAF6 and TRAF3 complex, leading to IFN and pro-inflammatory production.

中文翻译：

诱导型LGALS3BP / 90K通过靶向TRAF6和TRAF3复合体来激活抗病毒先天免疫应答。

galectin 3结合蛋白（LGALS3BP，也称为90K）是最初在癌症进展中发现的普遍存在的多功能分泌糖蛋白。尚不清楚90K在病毒感染过程中在先天免疫中如何发挥作用。在这项研究中，我们发现病毒感染导致90K水平升高。进一步的研究表明90K的表达通过诱导IFN和促炎性细胞因子的产生而抑制了病毒的复制。在调查此事件背后的机制后，我们发现90K充当支架蛋白/衔接蛋白与TRAF6，TRAF3，TAK1和TBK1相互作用。此外，90K增强了TRAF6和TRAF3的泛素化，并作为TRAF6的特异性泛素化底物，导致转录因子NF-κB，IRF3和IRF7从细胞质转移到细胞核。结论：

更新日期：2019-08-13

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