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Study on oxygen-dependent translational control for metabolic regulation

Research Project

Project/Area Number 18K05421
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38020:Applied microbiology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Matsuyama Akihisa  国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (90399444)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords翻訳 / 翻訳後修飾 / 翻訳制御 / 代謝
Outline of Final Research Achievements

eIF5A is an essential protein that promotes the translation of proteins with specific amino acid sequences. eIF5A undergoes a specific post-translational modification called hypusination. This modification occurs in a two-step reaction, and in yeast, the second step (hydroxylation of deoxyhypusine) is not essential for growth, but is postulated to function as a sensor of oxygen concentration.
In this study, non-labeled proteomics was used to screen for proteins whose expression levels are reduced in the mmd1 disruptant showing defective hypusination, and more than 30 proteins were identified, indicating that hydroxylation of the eIF5A hypusine residue is involved in the translation of these proteins.

Academic Significance and Societal Importance of the Research Achievements

スペルミンやスペルミジン等のポリアミンは、老化に伴って細胞内濃度が減少する一方、癌細胞では高濃度で存在することが知られており、健康寿命や癌との関連性が示唆されている。eIF5Aはスペルミジンを基質として、その活性に必須なハイプシン化修飾を受ける唯一のタンパク質であり、癌の転移などにも重要であることから、老化や癌の研究において重要な研究対象となっている。これまでの研究はeIF5Aそのもの、あるいはハイプシン化の一段階目の反応に注目したものばかりである一方、本研究では二段階目の水酸化反応により制御を受けるタンパク質を同定したことから、eIF5Aの機能の全容を明らかにする手掛かりとなると考えられる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2023 2019 2018

All Presentation (3 results) (of which Int'l Joint Research: 2 results) Book (1 results)

  • [Presentation] 分裂酵母の新規染色体挿入型ベクターの開発2023

    • Author(s)
      松山晃久、橋本敦史、西村慎一、吉田稔
    • Organizer
      日本農芸化学会2023年度大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of NanoBiT-based 2- and 3-hybrid system in fission yeast2019

    • Author(s)
      Akihisa Matsuyama, Minoru Yoshida
    • Organizer
      2019 Cold Spring Harbor Asia Conference on Chemical Biology and Drug Discovery
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive analysis of the mechanism of action of theonellamides, marine-derived antifungals, based on fission yeast ORFeome2019

    • Author(s)
      Shinichi Nishimura, Akifumi Suganaga, Akihisa Matsuyama, Minoru Yoshida
    • Organizer
      2019 Cold Spring Harbor Asia Conference on Chemical Biology and Drug Discovery
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Book] 生体の科学2018

    • Author(s)
      松山晃久・吉田稔
    • Total Pages
      523
    • Publisher
      医学書院
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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