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Funational analysis of Rfu1 that regulates ubiquitin homeostasis

Research Project

Project/Area Number 23570184
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KIMURA Yoko  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (80291152)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsユビキチン / エンドソーム / Bro1 / Rfu1 / 蛋白質分解 / ユビキチンリガーゼ / 脱ユビキチン化酵素 / ホメオスタシス / Rsp5 / ubiquitin / 熱ショックストレス / endosome / Alix
Research Abstract

Yeast Rfu1 (Regulator for free ubiquitin chain 1) localizes to endosomes and plays a role in ubiquitin homeostasis by inhibiting the activity of Doa4. We showed that Bro1 that recruits Doa4 to endosomes and stimulates Doa4 deubiquitinating activity, also recruits Rfu1 to endosomes. This recruitment is mediated by a direct interaction between the YPEL motif in the Rfu1 carboxyl-terminus and the V domain in Bro1. Furthermore, overexpression of Bro1, particularly the V domain, prevents Rfu1 degradation in response to heat shock. Thus, Bro1 regulates both the localization and stability of Rfu1. Rfu1 degradation involved the proteasome and a ubiquitin ligase Rsp5, suggesting that Rfu1 stability is regulated by ubiquitin-proteasome pathways.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (18 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system2013

    • Author(s)
      Kimura Y, Fukushi J., Hori S., Matsuda N., Okatsu K. Kakiyama Y., Kawawaki J. Kakizuka A., and Tanaka K.
    • Journal Title

      Genes to Cells

      Volume: 18 Pages: 1131-1143

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Different dynamic movements of wild-type and pathogenic VCPs and the ir cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system2013

    • Author(s)
      Yoko Kimura, Junpei Fukushi, Seiji Hori, Noriyuki Matsuda, Kei Okatsu, Yukie Kakiyama, Junko Kawawaki, Akira Kakizuka, Keiji Tanaka
    • Journal Title

      Genes to Cells

      Volume: 18 Issue: 12 Pages: 1131-43

    • DOI

      10.1111/gtc.12103

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rescue of growth defects of yeast cdc48 mutants by pathogenic IBMPFD-VCPs2012

    • Author(s)
      Takata T, Kimura Y, Ohnuma Y, Kawawaki J, Kakiyama Y, Tanaka K, and Kakizuka A.
    • Journal Title

      J. Struct. Biol.

      Volume: 179 Pages: 93-103

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Huntingtin aggregation kinetics and their pathological role in a Drosophila Huntington's disease model2012

    • Author(s)
      Weiss K, Kimura Y, Lee W, and Littleton T.
    • Journal Title

      Genetics

      Volume: 190 Pages: 581-600

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rescue of growth defects of yeast cdc48 mutants by pathogenic IBMPFD-VCPs.2012

    • Author(s)
      Takata T et al.
    • Journal Title

      J. Str. Biology

      Volume: 173 Issue: 2 Pages: 93-103

    • DOI

      10.1016/j.jsb.2012.06.005

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Huntingtin aggregation kinetics and their pathological role in a Drosophila Huntington’s disease model.2012

    • Author(s)
      Weiss K, Kimura Y., Lee W, and Littleton T.
    • Journal Title

      Genetics

      Volume: 190 Issue: 2 Pages: 581-600

    • DOI

      10.1534/genetics.111.133710

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 脱ユビキチン化酵素の制御機構2011

    • Author(s)
      木村洋子
    • Journal Title

      実験医学

      Volume: 29 Pages: 1945-1949

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] ユビキチンホメオスタシスの制御機構2013

    • Author(s)
      木村洋子
    • Organizer
      第86回日本生化学会大会シンポジウム「タンパク質の品質管理と疾患」
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-13
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 単量体ユビキチンの量を制御するRfu1の局在と分解はBro1に依存している2013

    • Author(s)
      木村洋子, 川脇純子, 柿山幸恵, 田中啓二
    • Organizer
      第46回酵母遺伝学フォーラム
    • Place of Presentation
      仙台
    • Year and Date
      2013-09-10
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Dynamics of normal and pathogenic p97/VCP upon mitochondria stress2013

    • Author(s)
      Yoko Kimura, Akira Kakizuka, and Keiji Tanaka.
    • Organizer
      1^<st> International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
    • Place of Presentation
      Tokyo Japan
    • Year and Date
      2013-02-01
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリアストレスにおける変異VCPの動態解析2012

    • Author(s)
      木村洋子, 垣塚彰, 田中啓二
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリアストレスにおけるVCPの動態解析2012

    • Author(s)
      木村洋子
    • Organizer
      新学術領域[修飾シグナル病]若手ワークショップ
    • Place of Presentation
      湯河原
    • Year and Date
      2012-10-04
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 疾患型VCPは酵母cdc48変異体の増殖欠損を抑圧する2012

    • Author(s)
      高田尚寛, 木村洋子, 大沼洋平, 川脇純子, 柿山幸恵, 田中啓二, 垣塚彰
    • Organizer
      第45回酵母遺伝学フォーラム
    • Place of Presentation
      京都
    • Year and Date
      2012-09-05
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Rescue of growth defects of yeast cdc48 mutants by pathogenic IBMPFD-VCPs2012

    • Author(s)
      Kimura Y., Takata, T., Kakizuka A., and Tanaka K.
    • Organizer
      FASEB Summer Research Conference(Ubiquitin and Cellular Regulation)Vermont Academy
    • Place of Presentation
      Saxtons River, Vermont, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリアストレスにおける正常型と疾患型VCPの動態変化2012

    • Author(s)
      木村洋子, 田中啓二
    • Organizer
      新学術領域「修飾シグナル病」研究交流会
    • Place of Presentation
      東京大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Rescue of growth defects of yeast cdc48 mutants by pathogenic IBMPFD-VCPs2012

    • Author(s)
      Kimura Y., Takata, T., Kakizuka A., and Tanaka K.
    • Organizer
      FASEB Summer Research Conference (Ubiquitin and Cellular Regulation)
    • Place of Presentation
      Saxtons River, Vermont, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Dynamics of normal and pathogenic p97/VCP upon mitochondria stress Oral presentation2011

    • Author(s)
      Yoko Kimura , Akira Kakizuka , and Keiji Tanaka.
    • Organizer
      The 9^<th> International Conference on AAA proteins
    • Place of Presentation
      Kumamoto, Japan
    • Year and Date
      2011-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 単量体のユビキチン量を制御する因子Rfu1の制御機構2011

    • Author(s)
      木村洋子, 川脇純子, 下田鮎美, 柿山幸恵, 田中啓二
    • Organizer
      第44会酵母遺伝学フォーラム
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] ユビキチンホメオスタシスの制御機構2011

    • Author(s)
      木村洋子
    • Organizer
      新学術領域「修飾シグナル病」第一回領域推進会議
    • Place of Presentation
      東京大学
    • Related Report
      2013 Final Research Report
  • [Presentation] ユビキチンホメオスタシスの制御機構2011

    • Author(s)
      木村洋子
    • Organizer
      新学術領域「修飾シグナル病」第2回研究交流
    • Place of Presentation
      東京大学 (若手ポスター発表会)
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulatory mechanism of ubiquitin homeostasis2011

    • Author(s)
      木村洋子
    • Organizer
      「奈良先端未来開拓コロキウム」シンポジウム
    • Place of Presentation
      奈良先端科学技術大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulatory mechanism of ubiquitin homeostasis2011

    • Author(s)
      木村洋子
    • Organizer
      「奈良先端未来開拓コロキウム」シンポジウム(招待講演)
    • Place of Presentation
      奈良
    • Related Report
      2011 Research-status Report
  • [Presentation] Dynamics of normal and pathogenic p97/VCP upon mitochondira stress2011

    • Author(s)
      Yoko Kimura, Akira Kakizuka Keiji Tanaka
    • Organizer
      The 9th International Conference on AAA proteins
    • Place of Presentation
      熊本
    • Related Report
      2011 Research-status Report
  • [Presentation] ミトコンドリアストレスにおける変異VCPの動態解析

    • Author(s)
      木村洋子、垣塚彰 田中啓二
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Dynamics of normal and pathogenic p97/VCP upon mitochondria stress

    • Author(s)
      Yoko Kimura, Akira Kakizuka, and Keiji Tanaka.
    • Organizer
      1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling.
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Book] タンパク質の品質管理と神経変性2014

    • Author(s)
      木村洋子, 垣塚彰
    • Publisher
      Annual Review 神経
    • Related Report
      2013 Final Research Report
  • [Book] Annual Review 神経 20142014

    • Author(s)
      木村洋子 垣塚彰
    • Total Pages
      6
    • Publisher
      中外医学社
    • Related Report
      2013 Annual Research Report
  • [Remarks] 蛋白質代謝研究室・木村

    • URL

      http://www.igakuken.or.jp/pro-meta/studies/kimura.html

    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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