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Elucidation of phosphorylation mechanism participate in nucreocytoplasmic shuttling and secretion of HMGB1

Research Project

Project/Area Number 25870990
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Functional biochemistry
Research InstitutionKyushu Institute of Technology (2014-2015)
Kurume University (2013)

Principal Investigator

Taira Junichi  九州工業大学, 大学院情報工学研究院, 助教 (20549612)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsHMGB1 / PP2A / 核移行シグナル / PKC / GSK-3 / CK2 / NLS / RAW264.7
Outline of Final Research Achievements

Phosphorylation of high mobility group box 1 (HMGB1) is involved in the subcellular translocation of the protein and subsequent secretion. Phosphorylation of serine residues in the two nuclear localization signals (NLS1 and NLS2) promotes nucleocytoplasmic relocation of HMGB1. In this study, it was suggested that protein phosphatase 2A (PP2A) correlates in the nucleocytoplasmic shuttling of HMGB1 through dephosphorylation of specific phosphoserines within NLS1. Next, kinases that phosphorylate serine residues within NLS1 were predicted, and an in vitro kinase assay was performed. Among the predicted kinases, protein kinase C phosphorylated Ser46 of HMGB1-derived peptides, and a mutagenesis experiment implied that the phosphorylation could induce translocation of HMGB1 to the cytosol.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (24 results)

All 2016 2015 2014 2013

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] EprS, an autotransporter serine protease, plays an important role in various pathogenic phenotypes of Pseudomonas aeruginosa2016

    • Author(s)
      Kida, Y., Taira, J., Kuwano, K.
    • Journal Title

      Microbiology

      Volume: 162 Issue: 2 Pages: 318-329

    • DOI

      10.1099/mic.0.000228

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples2015

    • Author(s)
      Junichi Taira, Yukinori Nakashima, Shun Yoshihara, Shinya Koga, Shinji Sueda, Hideyuki Komatsu, Yuichiro Higashimoto, Toru Takahashi, Nohito Tanioka, Hiroko Shimizu, Hiroshi Morimatsu, Hiroshi Sakamoto
    • Journal Title

      Analytical Biochemistry

      Volume: 489 Pages: 50-52

    • DOI

      10.1016/j.ab.2015.08.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pigment epithelium derived factor inhibits caveolin induced interleukin 8 gene expression and proliferation of human prostate cancer cells.2015

    • Author(s)
      T. Matsui, A. Ojima, Y. Higashimoto, J. Taira, K. Fukami, S. Yamagishi
    • Journal Title

      Oncology Letters

      Volume: 10 Pages: 2644-2648

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of InhA inhibitors with anti-mycobacterial activity through a matched molecular pair approach.2015

    • Author(s)
      Kanetaka H, Koseki Y, Taira J, Umei T, Komatsu H, Sakamoto H, Gulten G, Sacchettini JC, Kitamura M, Aoki S.
    • Journal Title

      Eur. J. Med. Chem.

      Volume: 94 Pages: 378-385

    • DOI

      10.1016/j.ejmech.2015.02.062

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming of Grb14 and insulin receptor.2014

    • Author(s)
      Taira J, Higashimoto Y
    • Journal Title

      J. Biochem.

      Volume: 印刷中

    • NAID

      40020088991

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of in vitro properties of predicted kinases that phosphorylate serine residues within nuclear localization signal 1 of high mobility group box 12014

    • Author(s)
      Taira J, Higashimoto Y
    • Journal Title

      J. Pept. Sci.

      Volume: 印刷中

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein phosphatase 2A dephosphorylates phosphoserines in nucleocytoplasmic shuttling and secretion of high mobility group box 12013

    • Author(s)
      Taira, J., Kida, Y., Kuwano, K., Higashimoto, Y.
    • Journal Title

      J. Biochem.

      Volume: 154 Issue: 3 Pages: 299-308

    • DOI

      10.1093/jb/mvt056

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blockade by phosphorothioate aptamers of advanced glycation end products-induced damage in cultured pericytes and endothelial cells2013

    • Author(s)
      Higashimoto, Y., Matsui, T., Nishino, Y., Taira, J., Inoue, H., Takeuchi, M., Yamagishi, S.I.
    • Journal Title

      Microvasc. Res.

      Volume: 90 Pages: 64-70

    • DOI

      10.1016/j.mvr.2013.08.010

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pigment epithelium-derived factor (PEDF) binds to caveolin-1 and inhibits the pro-inflammatory effects of caveolin-1 in endothelial cells2013

    • Author(s)
      Matsui T, Higashimoto Y, Taira J, Yamagishi S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 441 Pages: 405-410

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Phosphorylations of Grb14 BPS domain by GSK-3 are correlated with complex forming between Grb14 and insulin receptor2015

    • Author(s)
      Junichi Taira, Yuichiro Higashimoto, Hiroshi Sakamoto
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, Hawaii
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quantification of free heme by using a sensor based on fluorescently labeled heme oxygenase-12015

    • Author(s)
      Yukinori Nakashima, Junichi Taira, Yuichiro Higashimoto, Sinji Sueda, Hideyuki Komatsu, Hiroshi Sakamoto
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, Hawaii
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 表面プラズモン共鳴法によるヘムオキシゲナーゼ2のN末端領域とNADPHチトクロムP450レダクターゼ間の相互作用解析2015

    • Author(s)
      平 順一, 和田翔太, 福嶋祐也, 末田慎二, 小松英幸, 杉島正一, 東元祐一郎, 坂本 寛
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      平塚中央公民館, 平塚市
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変異NADPH-シトクロムP450還元酵素(CPR)を用いたCPRからヘムオキシゲナーゼへの電子伝達機構の解明2015

    • Author(s)
      杉島正一, 平 順一, 佐藤秀明, 野口正人, 山本 健, 坂本 寛
    • Organizer
      第39回タンパク質の構造と機能に関する九州シンポジウム
    • Place of Presentation
      豊泉荘, 別府市
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Grb14 BPSドメイン内部のリン酸化はインスリン受容体との複合体形成に影響する2015

    • Author(s)
      平 順一, 東元祐一郎, 坂本 寛
    • Organizer
      平成27年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学箱崎キャンパス, 福岡市
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヘムオキシゲナーゼ-1を基盤としたヘムセンサーによる生体試料中の遊離ヘムの定量2015

    • Author(s)
      平 順一, 中島幸徳, 義原 俊, 古賀真也, 末田慎二, 小松英幸, 東元祐一郎, 坂本 寛
    • Organizer
      平成27年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学箱崎キャンパス, 福岡市
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Effect of glycogen synthase kinase 3 on the complex forming between growth factor receptor bound protein 14 and insulin receptor2014

    • Author(s)
      平順一, 坂本 寛, 東元祐一郎
    • Organizer
      第51回ペプチド討論会
    • Place of Presentation
      徳島大学(徳島市)
    • Year and Date
      2014-10-22 – 2014-10-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of a heme sensor using fluorescent-labeled heme oxygenase-12014

    • Author(s)
      Koga S, Nakashima Y, Higashimoto Y, Sueda S, Komatsu H, Taira J, Sakamoto H
    • Organizer
      8th International Conference on Heme Oxygenases, BioIron and Oxydative Stress
    • Place of Presentation
      Sydney
    • Year and Date
      2014-10-08 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Grb14とインスリン受容体の複合体形成におけるリン酸化の影響評価2014

    • Author(s)
      平順一, 東元祐一郎
    • Organizer
      第38回 タンパク質と酵素の構造と機能に関する九州シンポジウム
    • Place of Presentation
      レイクサイドホテル久山(久山町)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Grb14によるインスリンシグナル抑制へのGSK-3の関与2014

    • Author(s)
      平順一, 東元祐一郎
    • Organizer
      平成26年度日本生化学会九州支部例会
    • Place of Presentation
      九州大学医系キャンパス(福岡市)
    • Year and Date
      2014-05-17 – 2014-05-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Grb14によるインスリン受容体の阻害へのGSK-3の関与2014

    • Author(s)
      平 順一, 東元 祐一郎
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス(名古屋市)
    • Related Report
      2013 Research-status Report
  • [Presentation] カベオリン1との相互作用によるプロテインホスファターゼ5の酵素活性の亢進2014

    • Author(s)
      東元 祐一郎, 平 順一
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス(名古屋市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Tyr誘導体の細胞毒性2013

    • Author(s)
      平 順一, 上田敏久, 宗 伸明, 関 清彦, 光富 勝
    • Organizer
      2013年度日本農芸化学会関西・中四国・西日本支部合同大会
    • Place of Presentation
      県立広島大学広島キャンパス(広島市)
    • Related Report
      2013 Research-status Report
  • [Presentation] カベオリン1はPC-3細胞中でプロテインホスファターゼ5と相互作用し内在性の活性化因子として作用する2013

    • Author(s)
      東元 祐一郎, 平 順一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 抗腫瘍活性を有するチロシン誘導体2014

    • Inventor(s)
      上田敏久, 宗 伸明, 光冨 勝, 関 清彦, 平 順一
    • Industrial Property Rights Holder
      佐賀大学, 久留米大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-040941
    • Filing Date
      2014-03-03
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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