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Identification of translational regulators of histone acetyltransferases

Research Project

Project/Area Number 19K16357
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionChiba Institute of Science

Principal Investigator

Sakamoto Akihiko  千葉科学大学, 薬学部, 助教 (10737290)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsヒストン修飾 / 遺伝子発現 / ヒストンアセチル化酵素 / ポリアミン / 翻訳
Outline of Research at the Start

生命現象の中心を担うと考えられるエピジェネティクスの異常により、がんをはじめとする多くの疾患との関連が報告されている。しかし、エピジェネティック異常の原因は解明されておらず、治療戦略を立てる上で、重要な課題である。本研究では、細胞増殖因子ポリアミンのヒストンアセチル化酵素発現制御機構を解析し、ポリアミンがヒストン修飾酵素の発現制御因子として活用できるか検討する。

Outline of Final Research Achievements

Polyamines regulate gene expression in Escherichia coli by stimulating translation of mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotic cells. Polyamines stimulate the translation of histone acetyltransferases Gcn5 and Hat1 at the level of translation, and regulate transcription of genes required for cell proliferation by enhancing histone acetylation.

Academic Significance and Societal Importance of the Research Achievements

エピジェネティックな遺伝子発現制御の一つであるヒストン修飾は、異常が起こると、がんなどの疾患の発症に寄与することが知られている。しかし、ヒストン修飾を担う修飾酵素の明確な制御因子は同定されていない。本研究では、細胞増殖因子ポリアミンがヒストンアセチル化酵素の翻訳制御因子であることを明らかにした。したがって、ヒストン修飾異常解明や新薬開発(創薬ターゲット)の基盤となる成果が得られた。

Report

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

    (17 results)

All 2021 2020 2019 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (2 results)

  • [Journal Article] Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines2021

    • Author(s)
      Sakamoto A, Terui Y, Uemura T, Igarashi K, Kashiwagi K.
    • Journal Title

      Int J Mol Sci.

      Volume: 22(3) Issue: 3 Pages: 1307-1307

    • DOI

      10.3390/ijms22031307

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs2020

    • Author(s)
      Sakamoto A, Terui Y, Uemura T, Igarashi K, Kashiwagi K.
    • Journal Title

      J Biol Chem.

      Volume: 295(26) Issue: 26 Pages: 8736-8745

    • DOI

      10.1074/jbc.ra120.013833

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural change and degradation of cytoskeleton due to the acrolein conjugation with vimentin and actin during brain infarction2020

    • Author(s)
      Uemura T, Suzuki T, Ko K, Nakamura M, Dohmae N, Sakamoto A, Terui Y, Toida T, Kashiwagi K, Igarashi K.
    • Journal Title

      Cytoskeleton (Hoboken)

      Volume: 77(10) Issue: 10 Pages: 414-421

    • DOI

      10.1002/cm.21638

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of an ELISA for Measurement of Urinary 3-Hydroxypropyl Mercapturic Acid (3-HPMA), the Marker of Stroke2020

    • Author(s)
      Sakamoto A, Uemura T, Terui Y, Yoshida M, Fukuda K, Nakamura T, Kashiwagi K, Igarashi K.
    • Journal Title

      Med Sci (Basel).

      Volume: 8(3) Issue: 3 Pages: 33-33

    • DOI

      10.3390/medsci8030033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 細胞増殖因子ポリアミンによるヒストンアセチル化酵素の翻訳促進2020

    • Author(s)
      坂本明彦
    • Journal Title

      月刊 細胞

      Volume: 52(9) Pages: 24-26

    • NAID

      40022799111

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic Mechanism of Excess Polyamines Functions through Translational Repression of Specific Proteins Encoded by Polyamine Modulon.2020

    • Author(s)
      Sakamoto A, Sahara J, Kawai G, Yamamoto K, Ishihama A, Uemura T, Igarashi K, Kashiwagi K, Terui Y.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 7 Pages: 2406-2406

    • DOI

      10.3390/ijms21072406

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of dendritic spine extension through acrolein conjugation with α-, β-tubulin proteins.2019

    • Author(s)
      Uemura T, Suzuki T, Ko K, Watanabe K, Dohmae N, Sakamoto A, Terui Y, Toida T, Kashiwagi K, Igarashi K.
    • Journal Title

      Int J Biochem Cell Biol.

      Volume: 113 Pages: 58-66

    • DOI

      10.1016/j.biocel.2019.05.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] ポリアミンは時計遺伝子を翻訳レベルで発現制御する2021

    • Author(s)
      坂本明彦, 照井祐介, 植村武史, 五十嵐一衛, 柏木 敬子
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アクロレイン毒性を指標とした脳梗塞予防効果を持つ食品成分の同定2021

    • Author(s)
      植村武史, 中村瑞穂, 坂本明彦, 照井祐介, 柏木敬子, 五十嵐一衛
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ポリアミンはヒストンアセチル化を促進して遺伝子発現を制御する2020

    • Author(s)
      坂本明彦, 照井祐介, 植村武史, 五十嵐一衛, 柏木敬子
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ポリアミンによる時計遺伝子Bmal1の合成促進機構解明2020

    • Author(s)
      岩崎倖千、坂本明彦、照井祐介、五十嵐一衛、柏木敬子
    • Organizer
      日本ポリアミン学会 第11回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 尿中アクロレイン代謝物3-HPMA測定法の開発2020

    • Author(s)
      坂本明彦、植村武史、照井祐介、柏木敬子、五十嵐一衛
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Polyamines enhance synthesis of the circadian regulator Bmal1 at translational level2019

    • Author(s)
      Akihiko Sakamoto, Sachi Iwasaki, Yusuke Terui, Takeshi Uemura, Kazuei Igarashi, Keiko Kashiwagi
    • Organizer
      Gordon Research Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inhibition of cell growth and viability by excess polyamines through translational repression of specific proteins encoded by members of polyamine modulon in Escherichia coli2019

    • Author(s)
      Yusuke Terui, Akihiko Sakamoto, Junpei Sahara, Gota Kawai, Takeshi Uemura, Kazuei Igarashi, Keiko Kashiwagi
    • Organizer
      Gordon Research Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞増殖因子スペルミジンの過剰蓄積が起こす細胞毒性の機序解析2019

    • Author(s)
      岩崎倖千、坂本明彦、佐原潤平、河合剛太、山本兼由、石浜明、植村武史、五十嵐一衛、柏木敬子、照井祐介
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 千葉科学大学 薬学部 病態生化学研究室

    • URL

      http://www.cis.ac.jp/~kkashiwagi/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Remarks] 千葉科学大学ホーム_教員検索_坂本 明彦

    • URL

      https://www.cis.ac.jp/teacher/detail/49

    • Related Report
      2020 Annual Research Report 2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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