PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation

Authors

Zexing Li, Chinese Academy of Sciences, China
Ge Liu, Chinese Academy of Sciences, China
Liwei Sun, Chinese Academy of Sciences, China
Yan Teng, Institute of Biotechnology, China
Xuejiang Guo, Nanjing Medical University, China
Jianhang Jia, University of KentuckyFollow
Jiahao Sha, Nanjing Medical University, China
Xiao Yang, Institute of Biotechnology, China
Dahua Chen, Chinese Academy of Sciences, China
Qinmiao Sun, Chinese Academy of Sciences, China

Abstract

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.

Document Type

Article

Publication Date

3-27-2015

Notes/Citation Information

Published in PLoS Pathogens, v. 11, no. 3, article e1004783, p. 1-26.

© 2015 Li et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Digital Object Identifier (DOI)

http://dx.doi.org/10.1371/journal.ppat.1004783

Funding Information

Funding: This work is supported by National Basic Research Program of China (2010CB945300 and 2010CB945000), and Natural Science Foundation of China (31370882). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Repository Citation

Li, Zexing; Liu, Ge; Sun, Liwei; Teng, Yan; Guo, Xuejiang; Jia, Jianhang; Sha, Jiahao; Yang, Xiao; Chen, Dahua; and Sun, Qinmiao, "PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation" (2015). Markey Cancer Center Faculty Publications. 34.
https://uknowledge.uky.edu/markey_facpub/34