title: AMAP1 as a negative-feedback regulator of nuclear factor-κB under inflammatory conditions.
abstract: NF-κB is a major transcriptional factor regulating many cellular functions including inflammation; therefore, its appropriate control is of high importance. The detailed mechanism of its activation has been well characterized, but that of negative regulation is poorly understood. In this study, we showed AMAP1, an Arf-GTPase activating protein, as a negative feedback regulator for NF-κB by binding with IKKβ, an essential kinase in NF-κB signaling. Proteomics analysis identified AMAP1 as a binding protein with IKKβ. Overexpression of AMAP1 suppressed NF-κB activity by interfering the binding of IKKβ and NEMO, and deletion of AMAP1 augmented NF-κB activity. The activation of NF-κB induced translocation of AMAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of AMAP1 and IKKβ. These results demonstrated a novel role of AMAP1 as a negative feedback regulator of NF-κB, and presented it as a possible target for anti-inflammatory treatments.
authors.affiliation: 1] Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan [2] Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan [3] Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Dat Nguyen
authors.initials: DN
authors.lastname: Tien
authors.affiliation: 1] Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan [2] Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kishihata
authors.affiliation: Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Yoshikawa
authors.affiliation: Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Ari
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Sabe
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nishi
authors.affiliation: Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Kaeko
authors.initials: K
authors.lastname: Kamei
authors.affiliation: Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.affiliation: 1] Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan [2] Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ashida
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D025461:Feedback, Physiological; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C491731:IKBKG protein, human; D016328:NF-kappa B; D051550:I-kappa B Kinase