Open AccessInducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex
Author(s) -
Gang Xu,
Zhangchuan Xia,
FeiYan Deng,
Lin Liu,
Qiming Wang,
Yi Yu,
Xinghuan Wang,
Chengliang Zhu,
Weiyong Liu,
Zhikui Cheng,
Ying Zhu,
Li Zhou,
Yi Zhang,
Mengji Lu,
Lei Shi
Publication year - 2019
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008002
Subject(s) - irf3 , signal transducing adaptor protein , innate immune system , microbiology and biotechnology , biology , trif , transcription factor , immune system , signal transduction , immunology , toll like receptor , biochemistry , gene
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.