1. Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling.
- Author
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Tan P, He L, Cui J, Qian C, Cao X, Lin M, Zhu Q, Li Y, Xing C, Yu X, Wang HY, and Wang RF
- Subjects
- ATPases Associated with Diverse Cellular Activities, Animals, Carrier Proteins genetics, Cell Line, Tumor, Chlorocebus aethiops, DEAD Box Protein 58 genetics, DNA-Binding Proteins genetics, Humans, Intracellular Signaling Peptides and Proteins, Mitochondria genetics, Mitochondrial Proteins genetics, Multiprotein Complexes genetics, Phosphoprotein Phosphatases genetics, Receptors, Immunologic, Signal Transduction genetics, Tripartite Motif Proteins, Vero Cells, Virus Diseases genetics, Virus Diseases immunology, Viruses genetics, Viruses immunology, Carrier Proteins immunology, DEAD Box Protein 58 immunology, DNA-Binding Proteins immunology, Immunity, Innate, Mitochondria immunology, Mitochondrial Proteins immunology, Multiprotein Complexes immunology, Phosphoprotein Phosphatases immunology, Signal Transduction immunology
- Abstract
Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP contributes to stabilization of the RIG-I-dsRNA interaction. Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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