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Temporal information coding of cell proliferation inhibitory signal revealed by optical measurement and control of p38 activity in living cells

Research Project

Project/Area Number 19K06548
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionToho University

Principal Investigator

Tomida Taichiro  東邦大学, 医学部, 講師 (70396886)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsストレス応答 / 癌細胞 / 増殖抑制 / キナーゼ / 定量 / 光操作 / シグナル伝達 / ストレス / 可視化 / p38MAPK / 光遺伝学 / 細胞増殖
Outline of Research at the Start

抗癌剤や炎症性サイトカインなどの刺激の種類に依存して、刺激を受けた細胞内シグナルは非常に動的な時間・空間的変動を示すことが明らかになっている。本研究では、p38の動的な挙動が癌細胞の増殖および増殖抑制の細胞内シグナルにどのように寄与するかを明らかにすることを目的とする。そのために、生細胞内のp38の酵素活性を任意の細胞内部位およびタイミングで人為的に誘導する新規の光操作実験系を構築し、これを用いて、細胞機能におけるp38動態の生理的意義を解明する。

Outline of Final Research Achievements

Human cells have pathways that contribute to growth suppression by induction of cell cycle arrest or cell death. In this study, we focused on growth suppressing stress-activated kinase p38 and proceeded with the development of a novel p38 activity reporter and optogenetic p38 control system for the purpose of understanding the regulatory mechanism of cell-growth suppressing signaling. As a result, I succeeded in constructing a new reporter that enables high-throughput signal detection even under condition without light irradiation. In addition, using this reporter, imaging analysis was performed on colon cancer-derived cells, and the temporal relationship between p38 activity and cell death was found.

Academic Significance and Societal Importance of the Research Achievements

近年、細胞内情報伝達分子の網羅的な解析技術が進み、増殖抑制に関わる分子の同定は数多く報告されているが、個々の分子が実際に生きた細胞内でどのように振る舞うかはほとんど明らかになっていない。本研究によって、さまざまな細胞種に普遍的に存在するp38分子が細胞死を誘導する際にどのような活性変動をするかを明らかにすることができた。さらに、その動的挙動と細胞機能との関連を解析するのに有用な光遺伝学的活性操作系も新規に構築することができた。これらの知見を活用することで、癌や異常免疫等に対する新たな診断法や治療法開発への応用が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2022 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Osmostress enhances activating phosphorylation of Hog1 MAP kinase by mono-phosphorylated Pbs2 MAP2K.2020

    • Author(s)
      Tatebayashi K, Yamamoto K, Tomida T, Nishimura A, Takayama T, Oyama M, Kozuka-Hata H, Adachi-Akahane S, Tokunaga Y, Saito H
    • Journal Title

      EMBO J

      Volume: 39 Issue: 5

    • DOI

      10.15252/embj.2019103444

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Gene regulation of excitation-contraction coupling initiated by cell-cell fusion of skeletal myogenesis2022

    • Author(s)
      Taichiro Tomida, Kimitaka Yamaguchi, Yoshinori Mikami, Daisuke Ohshima, Satomi Adachi-Akahane
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Gene regulation by cell-cell fusion in skeletal myogenesis2022

    • Author(s)
      Taichiro Tomida, Kimitaka Yamaguchi, Yoshinori Mikami, Daisuke Ohshima, Satomi Adachi-Akahane
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Regulatory mechanism of cell fusion in skeletal myogenesis2020

    • Author(s)
      Taichiro Tomida, Kimitaka Yamaguchi, Masanori Ito, Yoshinori Mikami, Daisuke Ohshima, Satomi Adachi-Akahane
    • Organizer
      2020年度生理研心血管国際研究集会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Temporal regulation of IL-1β induced JNK signaling dynamics2020

    • Author(s)
      Taichiro Tomida, Kimitaka Yamaguchi, Masanori Ito, Yoshinori Mikami, Daisuke Ohshima, Satomi Adachi-Akahane
    • Organizer
      第97回生理学会大会(誌上開催)
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-12-25  

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