TY - JOUR
T1 - PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation
AU - Li, Zexing
AU - Liu, Ge
AU - Sun, Liwei
AU - Teng, Yan
AU - Guo, Xuejiang
AU - Jia, Jianhang
AU - Sha, Jiahao
AU - Yang, Xiao
AU - Chen, Dahua
AU - Sun, Qinmiao
N1 - Publisher Copyright:
© 2015 Li et al.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1004783
DO - 10.1371/journal.ppat.1004783
M3 - Article
C2 - 25815785
AN - SCOPUS:84926450646
SN - 1553-7366
VL - 11
SP - 1
EP - 26
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 3
M1 - e1004783
ER -