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Development of Small GTPase with Photoswitching system and its application to photocontrol of intramolecular cell signaling

Research Project

Project/Area Number 15K07060
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionSoka University

Principal Investigator

Maruta Shinsaku  創価大学, 理工学部, 教授 (40231732)

Research Collaborator UMEKI NOBUHISA  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords低分子量Gタンパク質 / 細胞内情報伝達 / 光制御 / フォトクロミック分子 / アゾベンゼン / 制御因子 / ペプチド / Ras
Outline of Final Research Achievements

Ras is one of the small GTPase that regulates key cell functions such as cell proliferation and differentiation, gene expression, and cell adhesion. In addition, mutations at the amino acids involved in GTP hydrolysis has been shown to induce canceration of cells. Since the structure of Ras and its molecular mechanism as a biomolecular machine have been well studied, it will be possible to control of cell function if Ras can be regulated by an artificial external stimulus utilizing the ingenious mechanism of Ras. In this study, we attempted to control the function of Ras reversibly by introducing photo responsive photochromic molecules as a light switch into the mechanical mechanism of Ras and the regulating factor of Ras. And we clarified that the GTPase activity of Ras is controlled reversibly. In addition, it was shown that this photochromic peptide can be used to control the GDP-GTP exchange reaction of Ras in a photoreversible manner.

Academic Significance and Societal Importance of the Research Achievements

本研究では、重要な生理機能を担う低分子量G-蛋白質Rasを、情報伝達系の生体分子機械として捉え、その分子機械的仕組みに積極的に外部刺激応答性ナノデバイスを導入して人工的外部刺激で、Rasの細胞内情報伝達機能が制御出来る事を示した。このことにより、細胞の増殖、分化を人工的外部刺激で調節することが可能になると期待される。このRasの情報伝達機能を人工的に制御する方法を確立することにより、他の細胞機能を調節している低分子量G-蛋白質ファミリーへの応用も可能となる。細胞機能全体を人工的に制御するこの研究により、分子細胞の研究分野ばかりではなく医療分野へ貢献できることが強く期待できる。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (41 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (33 results) (of which Int'l Joint Research: 15 results) Remarks (2 results)

  • [Int'l Joint Research] University of Texas at Tyler(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Texas at Tyler(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] テキサス大学 Health Northeast(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Texas(U.S.A.)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Interaction of a Novel Fluorescent GTP Analogue with the small G-protein K-Ras2016

    • Author(s)
      Seigo IWATA, Kaori MASUHARA, Nobuhisa UMEKI, Yasushi SAKO and Shinsaku MARUTA
    • Journal Title

      The Journal of Biochemistry

      Volume: 159 Issue: 1 Pages: 41-48

    • DOI

      10.1093/jb/mvv071

    • NAID

      40020725621

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Photocontrol of the GTPase activity of the small G protein K-Ras by using an azobenzene2015

    • Author(s)
      Seigo IWATA and Shinsaku MARUTA
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 4 Pages: 268-276

    • DOI

      10.1016/j.bbrep.2015.10.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] PHOTO-CONTROL OF SMALL GTPASE RAS GDP-GTP EXCHANGE REACTION USING NOVEL PEPTIDE INHIBITOR MODIFIED WITH AZOBENZENE DERIVATIVES2019

    • Author(s)
      Nobuyuki Nishibe, Masahiro Kuboyama, Kenichi Taii,Toshio Nagashima, Toshio Yamazaki and Shinsaku Maruta
    • Organizer
      第63回米国生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PHOTO-CONTROL OF SMALL GTPASE RAS USING PHOTO RESPONSIVE PEPTIDE INHIBITOR WHICH MIMIC ΑH HELIX OF SOS2019

    • Author(s)
      Masahiro Kuboyama, Nobuyuki Nishibe, Kenichi Taii, Toshio Nagashima, Toshio Yamazaki, Kazunori Kondo and Shinsaku Maruta
    • Organizer
      第63回米国生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PHOTO-CONTROL OF RAS GDP-GTP EXCHANGE USING THE SOSΑH MIMICKING PEPTIDES MODIFIED WITH SPIROPYRAN DERIVATIVE2019

    • Author(s)
      Kenichi Taii, Nobuyuki Nishibe, Kei Sadakane and Shinsaku Maruta
    • Organizer
      第63回米国生物物理学会年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Photo-control of Small GTPase Ras Using Novel Photochromic Peptide Inhibitor2018

    • Author(s)
      Nobuyuki Nishibe, Kenichi Taii, Masahiro Kuboyama, Toshio Nagashima, Toshio Yamazaki and Shinsaku Maruta
    • Organizer
      平成30年度日本生化学会関東支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Photo-regulation of Small GTPase Ras Using Peptide Modified with Azobenzene2018

    • Author(s)
      Masahiro Kuboyama, Nobuyuki Nishibe, Taii Kenichi, Kondo Kazunori and Shinsaku Maruta
    • Organizer
      平成30年度日本生化学会関東支部例会 平成30年6月23日 埼玉
    • Related Report
      2018 Annual Research Report
  • [Presentation] Photo-control of Ras GDP-GTP exchange using the peptide modified with spiropyran derivative2018

    • Author(s)
      Kenichi Taii , Nobuyuki Nishibe and Shinsaku Maruta
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Photo-regulation of Small GTPase Ras using Photochromic SOS-Peptide2018

    • Author(s)
      Masahiro Kuboyama, Nobuyuki Nishibe, Kenichi Taii, Kazunori Kondo and Shinsaku Maruta
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HVR domain of small GTPase Ras changes its conformation in GTPase cycle2018

    • Author(s)
      久保山 正浩, 西部 伸幸, 梅木 伸久, 杉本 泰信, 丸田 晋策
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Photo-control of Small GTPase Ras Using Photochromic Peptide Inhibitors2018

    • Author(s)
      西部 伸幸, 泰井 賢一, 久保山 正浩, 長島 敏雄, 山崎 俊夫, 丸田 晋策
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PHOTO REGULATION OF SMALL G-PROTEIN RAS USING PHOTOCHROMIC PEPTIDE2018

    • Author(s)
      Masahiro Kuboyama, Nobuyuki Nishibe, Kazuo Fujiwara, Kazu- nori Kondo and Shinsaku Maruta
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] PHOTO CONTROL OF SMALL G PROTEIN RAS USING THE SYNTHETIC PEP- TIDE MODIFIED WITH WATER SOLUBLE AZOBENZENE2018

    • Author(s)
      Nobuyuki Nishibe, Masahiro Kuboyama, Kenichi Taii, Toshio Nagashima, Toshio Yamazaki and Shinsaku Maruta
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] CONFORMATIONAL CHANGE OF HVR DOMAIN OF SMALL GTPASE RAS REFLECTING PHYSIOLOGICAL FUNCTION2018

    • Author(s)
      Takashi Hashimoto, Nobuhisa Umeki, Yasunobu Sugimoto and Shinsaku Maruta
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] MORELLOFLAVONE AS A NOVEL INHIBITOR FOR KINESIN EG52018

    • Author(s)
      Tomisin Happy Ogunwa, Kenichi Taii, Shuya Yano, Kei Sadakane, Yuka Kawata, Shinsaku Maruta and Takayuki Miyanishi
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] NOVEL PHOTOCHROMIC POTENT INHIBITOR OF MITOTIC KINESIN EG5 COMPOSED OF SPIROPYRAN DERIVATIVES2018

    • Author(s)
      Kei Sadakane, Kenichi Taii and Shinsaku Maruta
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] PHOTO-REGULATION OF MITOTIC KINESIN EG5 USING NOVEL PHOTO- CHROMIC INHIBITOR THAT FORMS THREE ISOMERIZATION STATES2018

    • Author(s)
      Islam M.D. Alrazi, Kei Sadakane and Shinsaku Maruta
    • Organizer
      第62回米国生物物理学会年会 (San Francisco, CA USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photo-Regulation of Small G Protein RhoA Signal Cascade used by Photochromic Molecules2017

    • Author(s)
      Kaori Masuhara, Masahiro Kuboyama, Nobuyuki Nishibe, Mitsuo Ikebe, Shinsaku Maruta
    • Organizer
      第61回米国生物物理学会年会
    • Place of Presentation
      New Orleans, LA USA
    • Year and Date
      2017-02-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Conformational Change with the Multimerization of Small GTPase Ras induced by Chemical Modification at HVR Domain2017

    • Author(s)
      Takashi Hashimoto, Yasunobu Sugimoto, Shinsaku Maruta
    • Organizer
      第61回米国生物物理学会年会
    • Place of Presentation
      New Orleans, LA USA
    • Year and Date
      2017-02-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photo Regualtion of Small G-Protein Ras Phtochromic Peptide2017

    • Author(s)
      Masahiro Kuboyama, Kaori Masuhara, Shinsaku Maruta, Kazunori Kondo, Kzuo Fujiwara
    • Organizer
      第61回米国生物物理学会年会
    • Place of Presentation
      New Orleans, LA USA
    • Year and Date
      2017-02-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel phtochromic inhibitor of kinesin composed of dronpa tandem dimer2017

    • Author(s)
      Kohei Uchida, Shinsaku Maruta
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Photo-regulation of small GTPase Ras using photochromic peptide2017

    • Author(s)
      Masahiro Kuboyama, Nobuyuki Nishibe, Kazuo Fujiwara, Kazuniri Kondo, Mitsuo Ikebe, Shinsaku Maruta
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Biochemical analysis on the effect of morelloflavone as a novel inhibitor of mitotic kinesin Eg52017

    • Author(s)
      Kenichi Taii, Tomisin Happy Ogunwa, Shuya Yano, Kei Sadakane, Shinsaku Maruta, and Takayuki Miyanishi
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Photoregulation of calmodulin using bifunctional photochromic compound2017

    • Author(s)
      Takayuki Ogiwara, Hideki Shishido and Shinsaku Maruta
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Interaction of HVR domain of small GTPase Ras with catalytic domain2017

    • Author(s)
      Takashi Hashimoto, Nobuhisa Umeki, Yasunobu Sugimoto and Shinsaku Maruta
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel phtochromic inhibitor of mitotic kinesin Eg5 composed of spiropyran and azobenzene2017

    • Author(s)
      Md Alrazi Islam, Ryouta Shimoyama and Shinsaku Maruta
    • Organizer
      第55回日本生物物理学会年会 (熊本)
    • Related Report
      2017 Research-status Report
  • [Presentation] Photo-Regulation of Small G Protein RhoA using Photochromic Molecules2016

    • Author(s)
      Kaori Masuhara, MasahiroKuboyama, Nobuyuki Nishibe, Shinsaku Maruta
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Photo-regulation of Small G-protein Ras using Photochromic Molecules2016

    • Author(s)
      Masahiro Kuboyama, Kaori Masuhara, Shinsaku Maruta
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Structure and Mechanism of the Multimerization of Small GTPase protein Ras induced by Chemical Modification at HVR Domain2016

    • Author(s)
      Takashi Hashimoto, Shinsaku Maruta, Yasunobu Sugimoto
    • Organizer
      第54回日本生物物理学会年会
    • Place of Presentation
      つくば
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Photo-regulation of small G protein RhoA using ROCK Peptide Modified with Photochromic Molecules2016

    • Author(s)
      Kaori Masuhara, Masahiro Kuboyama, Nobuyuki Nishibe, Mitsuo Ikebe, Shinsaku Maruta
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] フォトクロミック分子を利用した低分子量Gタンパク質Rasの光制御2016

    • Author(s)
      久保山正浩, 丸田晋策
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] PHOTOREGULATION OF SMALL G-PROTEINS USING PHOTOCHROMIC MOLECULES2016

    • Author(s)
      Masahiro Kuboyama, Kaori Masuhara, Seigo Iwata, Shinsaku Maruta
    • Organizer
      第60回米国生物物理学会年会
    • Place of Presentation
      Los Angels, CA USA
    • Year and Date
      2016-03-01
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] PHOTOCONTROL OF SMALL G-PROTEIN H-RAS MULTIMER FORMATION USING CAGED COMPOUNDS2016

    • Author(s)
      Seigo Iwata, Takashi Hashimoto, Nobuhisa Umeki, Yasunobu Sugimoto, Kazunori Kondo, Shinsaku Maruta
    • Organizer
      第60回米国生物物理学会年会
    • Place of Presentation
      Los Angels, CA USA
    • Year and Date
      2016-02-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] PHTO-REGULATION of SMALL G PROTEIN RhoA USINGROCK PEPTIDE MODIFIED WITH PHOTOCHROMIC MOLECULES2016

    • Author(s)
      Kaori Masuhara, Masahiro Kuboyama, Mitsuo Ikebe, Shinsaku Maruta
    • Organizer
      第60回米国生物物理学会年会
    • Place of Presentation
      Los Angels, CA USA
    • Year and Date
      2016-02-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photo-regulation of small G protein RhoA using photochromic molecules2015

    • Author(s)
      Masahiro Kuboyama, Kaori Masuhara, Shinsa Maruta
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Remarks] 平成26年度理工学部国際共同研究報告

    • URL

      http://www.t.soka.ac.jp/maruta-lab/h26_oversea.html

    • Related Report
      2015 Research-status Report
  • [Remarks] H27年度科研費基盤研究Cが採択されました。

    • URL

      http://www.t.soka.ac.jp/maruta-lab/20150401.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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