PPM1B negatively regulates antiviral response via dephosphorylating TBK1.
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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, Yang J
PPM1B negatively regulates antiviral response via dephosphorylating TBK1.
Cell Signal. 2012 Nov;24(11):2197-204. doi: 10.1016/j.cellsig.2012.06.017. Epub 2012 Jun 30.
- PubMed ID
- 22750291 [ View in PubMed]
- 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 IFNbeta production. Our study identifies a previously unrecognized role for PPM1B in the negative regulation of antiviral response by acting as a TBK1 phosphatase.