title: hCINAP negatively regulates NF-κB signaling by recruiting the phosphatase PP1 to deactivate IKK complex.
abstract: Tight regulation of nuclear factor-κB (NF-κB) signaling is essential to maintain homeostasis in immune system in response to various stimuli, which has been studied extensively and deeply. However, the molecular mechanisms responsible for its negative regulation are not completely understood. Here we demonstrate that human coilin-interacting nuclear ATPase protein (hCINAP) is a novel negative regulator in NF-κB signaling by deactivating IκB kinase (IKK) complex. In response to TNF stimulation, hCINAP dynamically associates with IKKα and IKKβ and inhibits IKK phosphorylation. Notably, hCINAP directly interacts with the catalytic subunits of protein phosphatase 1 (PP1) and mediates the formation of IKK-hCINAP-PP1 complex, serving as an adaptor protein that recruits PP1 to dephosphorylate IKK. Furthermore, decreased levels of hCINAP are observed in several inflammatory diseases with NF-κB hyperactivity. Our study suggests a novel mechanism underlying deactivation of IKK and provides new insight into the negative regulation of NF-κB signaling.
authors.affiliation: State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Linglong
authors.initials: L
authors.lastname: Qu
authors.affiliation: State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Lab of Protein and Plant Gene Research, Beijing 100871, China Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China xiaofengz@pku.edu.cn.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D007107:Immune System / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C432963:TSPYL2 protein, human; D014409:Tumor Necrosis Factor-alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D054645:Protein Phosphatase 1
keywords: IKK complex; NF-κB; hCINAP; inflammatory diseases; phosphatase PP1