1. PPM1B negatively regulates antiviral response via dephosphorylating TBK1.
- Author
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Zhao Y, Liang L, Fan Y, Sun S, An L, Shi Z, Cheng J, Jia W, Sun W, Mori-Akiyama Y, Zhang H, Fu S, and Yang J
- Subjects
- DNA Replication, HEK293 Cells, HeLa Cells, Humans, Interferon Regulatory Factor-3 metabolism, Interferon-beta genetics, Interferon-beta metabolism, Phosphoprotein Phosphatases antagonists & inhibitors, Phosphoprotein Phosphatases genetics, Phosphorylation, Protein Binding, Protein Phosphatase 2C, RNA Interference, RNA, Small Interfering metabolism, Vesiculovirus genetics, Vesiculovirus metabolism, Phosphoprotein Phosphatases metabolism, Protein Serine-Threonine Kinases metabolism
- Abstract
The production of type I interferon must be tightly regulated and aberrant production of type I interferon is harmful or even fatal to the host. TBK1 phosphorylation at Ser172 plays an essential role in TBK1-mediated antiviral response. However, how TBK1 activity is negatively regulated remains poorly understood. Using a functional genomics approach, we have identified PPM1B as a TBK1 phosphatase. PPM1B dephosphorylates TBK1 in vivo and in vitro. PPM1B wild-type but not its phosphatase-deficient R179G mutant inhibits TBK1-mediated antiviral response and facilitates VSV replication in the cells. Viral infection induces association of PPM1B with TBK1 in a transient fashion in the cells. Conversely, suppression of PPM1B expression enhances virus-induced IRF3 phosphorylation and IFNβ production. Our study identifies a previously unrecognized role for PPM1B in the negative regulation of antiviral response by acting as a TBK1 phosphatase., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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