title: (DEAD)-box RNA helicase 3 modulates NF-κB signal pathway by controlling the phosphorylation of PP2A-C subunit.
abstract: Asp-Glu-Ala-Asp (DEAD)-box RNA helicase 3 (DDX3), an ATP-dependent RNA helicase, is associated with RNA splicing, mRNA export, transcription, translation, and RNA decay. Recent studies revealed that DDX3 participates in innate immune response during virus infection by interacting with TBK1 and regulating the production of IFN-β. In our studies, we demonstrated that DDX3 regulated NF-κB signal pathway. We found that DDX3 knockdown reduced the phosphorylation of p65 and IKK-β and ultimately attenuated the production of inflammatory cytokines induced by poly(I:C) or TNF-α stimulation. The regulatory effect of DDX3 on NF-κB signal pathway was not affected by the loss of its ATPase or helicase activity. We further identified PP2A C subunit (PP2A-C) as an interaction partner of DDX3 by co-immunoprecipitation and mass spectrum analysis. We confirmed that DDX3 formed the complex with PP2A-C/IKK-β and regulated the interaction between IKK-β and PP2A-C. Furthermore, we demonstrated that DDX3 modulated the activity of PP2A by controlling the phosphorylation of PP2A-C, which might enable PP2A-C to regulate NF-κB signal pathway by dephosphorylating IKK-β. All these findings suggested DDX3 plays multiple roles in modulating innate immune system.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Luo
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Hua-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
authors.forename: Chang-Chao
authors.initials: CC
authors.lastname: Huan
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Mao
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D021122:Protein Subunits; D054648:Protein Phosphatase 2; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
keywords: (DEAD)-box RNA helicase 3; NF-κB; PP2A