PPM1B negatively regulates antiviral response via dephosphorylating TBK1 |
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Authors: | Zhao Yanling Liang Li Fan Yihui Sun Surong An Lei Shi Zhongcheng Cheng Jin Jia Wei Sun Wenjing Mori-Akiyama Yuko Zhang Hong Fu Songbin Yang Jianhua |
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Institution: | Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China; Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. |
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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. |
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