PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting ST...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2015-03, Vol.11 (3), p.e1004783-e1004783
Main Authors: Li, Zexing, Liu, Ge, Sun, Liwei, Teng, Yan, Guo, Xuejiang, Jia, Jianhang, Sha, Jiahao, Yang, Xiao, Chen, Dahua, Sun, Qinmiao
Format: Article
Language:English
Subjects:
Animals
Cellular signal transduction
Chlorocebus aethiops
Deoxyribonucleic acid
DNA
Endoplasmic reticulum
Experiments
HEK293 Cells
HeLa Cells
Host-parasite relationships
Humans
Identification and classification
Immune system
Infections
Inflammatory diseases
Kinases
Membrane Proteins - genetics
Membrane Proteins - immunology
Mice
Mice, Knockout
Phosphatase
Phosphoprotein Phosphatases - genetics
Phosphoprotein Phosphatases - immunology
Phosphorylation
Phosphorylation - genetics
Phosphorylation - immunology
Protein Phosphatase 2C
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - immunology
Proteins
Regulation
Signal transduction
Signal Transduction - genetics
Signal Transduction - immunology
Vero Cells
Viral infections
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our findings demonstrate a novel regulatory circuit in which STING and TBK1 reciprocally regulate each other to enable efficient antiviral signaling activation, and PPM1A dephosphorylates STING and TBK1, thereby balancing this antiviral signal transduction.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004783