title: PPM1B negatively regulates antiviral response via dephosphorylating TBK1.
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.
authors: Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
authors: Yanling
authors: Y
authors: Zhao
authors: Li
authors: L
authors: Liang
authors: Yihui
authors: Y
authors: Fan
authors: Surong
authors: S
authors: Sun
authors: Lei
authors: L
authors: An
authors: Zhongcheng
authors: Z
authors: Shi
authors: Jin
authors: J
authors: Cheng
authors: Wei
authors: W
authors: Jia
authors: Wenjing
authors: W
authors: Sun
authors: Yuko
authors: Y
authors: Mori-Akiyama
authors: Hong
authors: H
authors: Zhang
authors: Songbin
authors: S
authors: Fu
authors: Jianhua
authors: J
authors: Yang
mesh_terms: D004261:DNA Replication; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D034741:RNA, Small Interfering; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C000607457:PPM1B protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C