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Establishment of method for identification of ubiquitinated protein

Research Project

Project/Area Number 17K19506
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical structure and function and related fields
Research InstitutionHokkaido University

Principal Investigator

Hatakeyama Shigetsugu  北海道大学, 医学研究院, 教授 (70294973)

Research Collaborator TAKAHASHI Hidehisa  横浜市立大学, 医学研究科, 教授 (20399819)
WATANABE Masashi  北海道大学, 医学研究院, 講師 (10632424)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsユビキチン / TRIM型E3 / TUBE / Parkin / 蛋白質 / シグナル伝達 / プロテオーム / 生体分子
Outline of Final Research Achievements

Ubiquitination is a chemical modification that controls protein degradation and is one of the most important post-translational modifications that support many biological phenomena. The reaction system is mediated by ubiquitin ligases (E3) selectively recognizing substrate proteins. Therefore, it is important to identify specific substrates of each E3 and to determine the ubiquitination site of substrate proteins in understanding the biological phenomenon that they are associated with. However, due to various problems, it is still far from standardizing ubiquitinated substrate identification methods. In this study, we challenged to establish a novel technology using TUBE (artificial protein exhibiting high affinity binding to polyubiquitin chain) and ubiquitin remnant antibody allows comprehensive application to various types of ubiquitin ligase (E3) and the E3-substrates relationship was analyzed.

Academic Significance and Societal Importance of the Research Achievements

本申請で開発した基質同定法は、これまでの問題点を原理的に解消した全く新しい手法であり、すべてのE3に対して適用可能であるため、E3の機能解析が加速することが期待できると思われる。本手法の応用により、正常及び異常(疾患)に関与しているユビキチン化修飾の全貌解明が期待できる。したがって、将来的には疾患特異的ユビキチン化部位を標的とした創薬のシーズを発掘できる可能性がある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma.2018

    • Author(s)
      Yanagi T, Watanabe M, Hata H, Kitamura S, Imafuku K, Yanagi H, Homma A, Wang L, Takahashi H, Shimizu H, Hatakeyama S.
    • Journal Title

      Cancer Res

      Volume: 78 Issue: 24 Pages: 6795-6806

    • DOI

      10.1158/0008-5472.can-18-1495

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure2018

    • Author(s)
      Matsumoto Junichi、et al. Hatakeyama Shigetsugu、Matsumoto Masaki、Nakayama Keiichi I.、Otsuka Yutaro、Sabe Hisataka、Tsutsui Hiroyuki、Anzai Toshihisa
    • Journal Title

      Circulation

      Volume: 138 Issue: 18 Pages: 2064-2066

    • DOI

      10.1161/circulationaha.118.035212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-Sez6l2 antibody, detected in a patient with immune-mediated cerebellar ataxia, inhibits complex formation of GluR1 and Sez6l22018

    • Author(s)
      Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., Watanabe, M. and Hatakeyama, S.
    • Journal Title

      J. Neurol.

      Volume: 265 Issue: 4 Pages: 962-965

    • DOI

      10.1007/s00415-018-8785-z

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] TRIM59 promotes gliomagenesis by inhibiting TC45 dephosphorylation of STAT32018

    • Author(s)
      Sang, Y., Li, Y., Song, L., Alvarez, A.A., Zhang, W., Lv, D., Tang, J., Liu, F., Chang, Z., Hatakeyama, S., Hu, B., Cheng, S. and Feng, H.
    • Journal Title

      Cancer Res.

      Volume: 78 Issue: 7 Pages: 1792-1804

    • DOI

      10.1158/0008-5472.can-17-2774

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome2018

    • Author(s)
      Yabe I, Yaguchi H, Kato Y, Miki Y, Takahashi H, Tanikawa S, Shirai S, Takahashi I, Kimura M, Hama Y, Matsushima M, Fujioka S, Kano T, Watanabe M, Nakagawa S, Kunieda Y, Ikeda Y, Hasegawa M, Nishihara H, Ohtsuka T, Tanaka S, Tsuboi Y, Hatakeyama S, Wakabayashi K, Sasaki H
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 819-819

    • DOI

      10.1038/s41598-018-19198-0

    • NAID

      120006377499

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM Family Proteins: Roles in Autophagy, Immunity and Carcinogenesis.2017

    • Author(s)
      Hatakeyama, S
    • Journal Title

      Trends Biochem. Sci.

      Volume: 42 Issue: 4 Pages: 297-311

    • DOI

      10.1016/j.tibs.2017.01.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fine-tuning of thymocyte development by ubiquitination-mediated stability control of the ESCRT protein CHMP52017

    • Author(s)
      Watanabe, M. and Hatakeyama, S.
    • Journal Title

      Cell. Moll. Immnol.

      Volume: 14 Issue: 12 Pages: 957-959

    • DOI

      10.1038/cmi.2017.91

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sez6l2 regulates phosphorylation of ADD and neuritogenesis2017

    • Author(s)
      Yaguchi, H., Yabe, I., Takahashi, H., Watanabe, M., Nomura, T., Kano, T., Matsumoto, M., Nakayama, K.I., Watanabe, M. and Hatakeyama, S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 494 Issue: 1-2 Pages: 234-241

    • DOI

      10.1016/j.bbrc.2017.10.047

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] TRIMファミリーの機能解析2019

    • Author(s)
      畠山鎮次
    • Organizer
      第2回ユビキチン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Comprehensive identification of E3 ubiquitin ligase substrates by fusion of TUBE and ligase trapping methods2018

    • Author(s)
      Masashi watanabe, Shigetsugu Hatakeyama
    • Organizer
      The 2nd GI-CoRE GSQ, GSB & IGM Joint Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] TRIMタンパク質の機能と病理学的解析2018

    • Author(s)
      畠山鎮次
    • Organizer
      第1回ユビキチン研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] TRIMファミリータンパク質が関与する疾患2017

    • Author(s)
      畠山鎮次
    • Organizer
      第24回分子皮膚科学フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] TRIMファミリータンパク質による細胞機能制御2017

    • Author(s)
      畠山鎮次
    • Organizer
      GU Cancer Forum 2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 人体の構造と機能[2] 生化学 第14版2019

    • Author(s)
      畠山 鎮次
    • Total Pages
      304
    • Publisher
      医学書院
    • ISBN
      9784260035569
    • Related Report
      2018 Annual Research Report

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Published: 2017-07-21   Modified: 2020-03-30  

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