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Function of ubiquitin-associated domain proteins for decoding polyubiquitin signaling.

Planned Research

Project AreaNew aspect of the ubiquitin system : its enormous roles in protein regulation
Project/Area Number 24112007
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Metropolitan University

Principal Investigator

Hiroyuki Kawahara  首都大学東京, 理工学研究科, 教授 (70291151)

Co-Investigator(Kenkyū-buntansha) 横田 直人  首都大学東京, 理工学研究科, 助教 (40610564)
Project Period (FY) 2012-06-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥82,810,000 (Direct Cost: ¥63,700,000、Indirect Cost: ¥19,110,000)
Fiscal Year 2016: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2015: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2013: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2012: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
Keywordsユビキチン / プロテアソーム / タンパク質の品質管理 / 膜タンパク質 / BAG6 / UBQLN4 / UBAドメイン / ポリユビキチン認識 / 細胞内タンパク質分解 / ユビキチン認識タンパク質 / ユビキチン結合蛋白質 / 蛋白質の品質管理 / ユビキチンコード / TRC複合体 / 分子シャペロン / 構造解析 / UBQLN / テイルアンカータンパク質 / ユビキチン識別タンパク質 / タンパク質品質管理 / アグリソーム / 凝集体形成 / UBA
Outline of Final Research Achievements

Most of transmembrane proteins are integrated into the ER by virtue of a signal sequence-mediated co-translational process. However, a substantial portion of transmembrane proteins fail to access the ER, resulting in the production of cytosolically mislocalized polypeptides. Their appropriate recognition and removal are of the utmost significance to avoid potential proteotoxic stress. Here, we identified UBA domain protein UBQLN4 for the elimination of such newly synthesized defective polypeptides. Using a model transmembrane domain protein whose degradation occurs at a pre-ER incorporation process, we show that UBQLN4 recognizes misassembled proteins in the cytoplasm for targeting to the proteasome pathway. Importantly, UBQLN4 recognized not only the model defective transmembrane substrate but also a pool of endogenous defective proteins that were induced by compromising the signal recognition particle.

Report

(6 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report

Research Products

(38 results)

All 2016 2015 2014 2013 2012 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (25 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] Cellular Molecular Pharmacology/School of Medicine/University of California, San Fransisco(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Faculty of Life Sciences/University of Manchester(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] UBQLN4 recognizes mislocalized transmembrane domain proteins and targets these to proteasomal degradation.2016

    • Author(s)
      Rigel Suzuki and Hiroyuki Kawahara
    • Journal Title

      EMBO Rep.

      Volume: 未定 Pages: 842-857

    • DOI

      10.15252/embr.201541402

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition.2016

    • Author(s)
      Tanaka, H., Takahashi, T., Xie, Y., Minami, R., Yanagi, Y., Hayashishita, M., Suzuki, R., Yokota, N., Shimada, M., Mizushima, T., Kuwabara, N., Kato, R., Kawahara, H.
    • Journal Title

      FEBS Journal

      Volume: 283 Pages: 662-667

    • DOI

      10.1111/febs.13618

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The C-terminal cytoplasmic tail of hedgehog receptor Patched1 is a platform for E3 ubiquitin ligase complexes.2016

    • Author(s)
      Yamaki, Y., Kagawa, H., Hatta, T., Natsume, T., and Kawahara, H.
    • Journal Title

      Mol Cell Biochem

      Volume: 414 Pages: 1-12

    • DOI

      10.1007/s11010-015-2643-4

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Two degradation pathways of the p35 Cdk5 activation subunit, dependent and independent of ubiquitination.2016

    • Author(s)
      Takasugi et al.,
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Pages: 4649-4657

    • DOI

      10.1074/jbc.m115.692871

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ユビキチンによるタンパク質品質管理と疾患2016

    • Author(s)
      川原裕之
    • Journal Title

      ユビキチンネオバイオロジーニュースレターThe World of UBIQUITIN

      Volume: 4 Pages: 60-64

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Structure of a BAG6 (Bcl-2-associated Athanogene 6)-Ubl4a (Ubiquitin-like Protein 4a) Complex Reveals a Novel Binding Interface That Functions in Tail-anchored Protein Biogenesis.2015

    • Author(s)
      Kuwabara N, Minami R, Yokota N, Matsumoto H, Senda T, Kawahara H, Kato R.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 290 Pages: 9387-9398

    • DOI

      10.1074/jbc.m114.631804

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BAG6/BAT3 : Emerging roles in quality control for nascent polypeptides2013

    • Author(s)
      Kawahara, H., Minami, R. and Yokota, N
    • Journal Title

      J. Biochem.

      Volume: 153 Pages: 147-160

    • DOI

      10.1093/jb/mvs149

    • NAID

      40019566398

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] ミトコンドリアを標的としたBAG6新規機能の探索2016

    • Author(s)
      林下瑞希、川原裕之
    • Organizer
      第39回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] BAG6は膜タンパク質Tim-3を量的に制御する2016

    • Author(s)
      坂山亮太、地主将久、川原裕之
    • Organizer
      第39回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミスローカライズしたHLAの代謝におけるBAG6の機能2016

    • Author(s)
      山本昂季、川原裕之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] UBQLN4による膜タンパク質品質管理機構の解明2016

    • Author(s)
      鈴木理滋、川原裕之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Patched1第7細胞質ドメイン結合タンパク質を介した新規Sonic hegdehogシグナル制御機構2016

    • Author(s)
      南雪也、川原裕之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] BAG6-Ubl4a複合体による不良膜タンパク質の品質管理機構2016

    • Author(s)
      戸島麻子、川原裕之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] BAG6による不良タンパク質認識機構の解明2016

    • Author(s)
      高橋俊樹、川原裕之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] ER膜に到達できなかった新合成膜タンパク質の運命:ユビキチン識別タンパク質による選択的認識と代謝2015

    • Author(s)
      川原 裕之
    • Organizer
      科研費新学術領域研究「ユビキチンネオバイオロジー」領域会議
    • Place of Presentation
      南房総富浦ロイヤルホテル(千葉県南房総市)
    • Year and Date
      2015-12-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Functional analysis of BAG6 and Ubl4a in Drosophila melanogaster.2015

    • Author(s)
      atanabe, A., Yokota, N., Takeo, S., Aigaki, T., and Kawahara, H.
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会合同年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] UBQLN is essential for quality control of mislocalized proteins.2015

    • Author(s)
      Suzuki, R. and Kawahara, H.
    • Organizer
      Cold Spring Harbor Meeting 2015, " The Ubiquitin Family ",
    • Place of Presentation
      Cold Spring Harbor (米国)
    • Year and Date
      2015-04-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] UBQLN4 is essential for the degradation of mislocalized membrane proteins.2014

    • Author(s)
      Rigel Suzuki and Hiroyuki Kawahara
    • Organizer
      International Meeting for New Aspects of the Ubiquitin Research
    • Place of Presentation
      International Institute for Advanced Studies
    • Year and Date
      2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] BAG6 modulates the localization and turnover of polytopic transmembrane receptor protein.2014

    • Author(s)
      Toshiki Takahashi and Hiroyuki Kawahara
    • Organizer
      International Meeting for New Aspects of the Ubiquitin Research
    • Place of Presentation
      International Institute for Advanced Studies
    • Year and Date
      2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNA-binding protein ZFP36L2 is controlled during the cell cycle2014

    • Author(s)
      Aya Noguchi, Naoto Yokota and Hiroyuki Kawahara
    • Organizer
      International Meeting for New Aspects of the Ubiquitin Research
    • Place of Presentation
      International Institute for Advanced Studies
    • Year and Date
      2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cullin-2-based E3 ligase functionally associates with hedgehog receptor Patched1.2014

    • Author(s)
      Yuka Yamaki, Hiroki Kagawa, Tomohisa Hatta, Yasushi Saeki, Tohru Natsume, Keiji Tanaka and Hiroyuki Kawahara
    • Organizer
      International Meeting for New Aspects of the Ubiquitin Research
    • Place of Presentation
      International Institute for Advanced Studies
    • Year and Date
      2014-11-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Post-mitotic degradation of ZFP36L1 and ZFP36L2 is under control of C-terminal phosphorylation.2014

    • Author(s)
      Aya Noguchi, Naoto Yokota, Hiroyuki Kawahara
    • Organizer
      Cold Spring Harbor Meeting 2014, The Cell Cycle
    • Place of Presentation
      Cold Spring Harbor laboratory
    • Year and Date
      2014-05-13 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] BAG6複合体による新しい新合成ポリペプチドの品質管理機構2013

    • Author(s)
      川原裕之
    • Organizer
      第86回日本生化学会大会シンポジウム
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2013-09-13
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] BAG6 is essential for selective elimination of aggregation-prone defective proteins.2013

    • Author(s)
      Hiroyuki Kawahara
    • Organizer
      The 35th Naito Conference
    • Place of Presentation
      ガトーキングダム札幌
    • Year and Date
      2013-07-09
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] BAG6 is essential for selective elimination of aggregation-prone defective proteins.2013

    • Author(s)
      Kawahara, H.
    • Organizer
      第35回内藤カンファレンス
    • Place of Presentation
      Sapporo
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] UBQLN4によるタンパク質品質管理機構2013

    • Author(s)
      鈴木 理滋, 福田 有里, 横田 直人, 川原 裕之
    • Organizer
      第86回 日本生化学会 年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規BAG6複合体構成因子の同定と解析2013

    • Author(s)
      林下 瑞希, 横田 直人, 川原 裕之
    • Organizer
      第86回 日本生化学会 年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヘッジホック受容体Patched 1と相互作用するユビキチン化酵素群の同定とその機能解析2013

    • Author(s)
      八巻 優佳,八田 知久,賀川 裕貴,佐伯 泰,夏目 徹,田中 啓二,川原 裕之
    • Organizer
      第36回 日本分子生物学会 年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] BAG6-プロテアソーム複合体を介した易凝集性タンパク質の品質管理2012

    • Author(s)
      川原裕之
    • Organizer
      第85回日本生化学会大会シンポジウム
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2012-12-14
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ユビキチン識別タンパク質複合体による新合成ポリペプチド鎖の品質管理2012

    • Author(s)
      川原裕之
    • Organizer
      新学術領域研究「ユビキチンネオバイオロジー:拡大するタンパク質制御システム」Kick-offシンポジウム
    • Place of Presentation
      京大医学部
    • Year and Date
      2012-09-26
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 易凝集性タンパク質の品質管理におけるBAG6複合体の役割2012

    • Author(s)
      川原裕之
    • Organizer
      第12回 日本蛋白質科学会 年会ワークショップ
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2012-07-21
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] BAG6複合体による新しい新合成ポリペプチドの品質管理機構

    • Author(s)
      川原裕之
    • Organizer
      第86回日本生化学会  シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 生化学 (分担執筆)2016

    • Author(s)
      川原裕之
    • Total Pages
      1
    • Publisher
      日本生化学会
    • Related Report
      2016 Annual Research Report
  • [Remarks] 首都大学東京 細胞生化学研究室ホームページ

    • URL

      http://www.comp.tmu.ac.jp/saisei/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 首都大学東京 生命科学教室ホームページ

    • URL

      http://www.biol.se.tmu.ac.jp/labo.asp?ID=celche

    • Related Report
      2016 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.biol.se.tmu.ac.jp/labo.asp?ID=celche

    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2022-01-31  

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