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Quality control system for the newly synthesized tail-anchored proteins.

Research Project

Project/Area Number 16K14699
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan University

Principal Investigator

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

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsBAG6 / ユビキチン / プロテアソーム / テイルアンカー蛋白質 / タンパク質品質管理 / タンパク質分解 / タンパク質凝集 / シグナル配列 / テイルアンカータンパク質 / BAG6複合体 / UBQLN4 / BUILDドメイン / 構造不良膜タンパク質 / TAタンパク質
Outline of Final Research Achievements

A portion of newly synthesized tail-anchored proteins tend to fail their correct assembly into the lumen of endoplasmic reticulum, thus resulting in the production of the defective species. Although the efficient degradation of these aggregation-prone polypeptides is crucial, the molecular mechanism of their elimination pathway has not been adequately characterized. In this study, we focused on one such cryptic portion of the defective transmembrane domain protein, and show that a part of these is produced as a labile species that is immediately targeted to the degradation pathway. We found that proteasomes are indispensable for elimination of mislocalized tail-anchored species. These observations suggest that protein degradation machinery acts as a critical factor for degradation of mislocalized tail-anchored proteins.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) Remarks (3 results)

  • [Int'l Joint Research] University of California, San Francisco(U.S.A.)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Mancester(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] マンチェスター大学/生物学教室(英国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] フランクフルト大学/医学部(ドイツ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] ZFP36L2 is a cell cycle-regulated CCCH protein necessary for DNA lesion-induced S-phase arrest2018

    • Author(s)
      Noguchi Aya、Adachi Shungo、Yokota Naoto、Hatta Tomohisa、Natsume Tohru、Kawahara Hiroyuki
    • Journal Title

      Biology Open

      Volume: 7

    • DOI

      10.1242/bio.031575

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities2018

    • Author(s)
      Xie Xuan、Matsumoto Shunsuke、Endo Akinori、Fukushima Toshiaki、Kawahara Hiroyuki、Saeki Yasushi、Komada Masayuki
    • Journal Title

      Journal of Cell Science

      Volume: 131 Issue: 8 Pages: 210856-210856

    • DOI

      10.1242/jcs.210856

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel phosphorelay-dependent control of ZFP36L1 protein during the cell cycle.2018

    • Author(s)
      Kondo, M., Noguchi, A., Matsuura, Y., Shimada, M., Yokota, N., Kawahara, H.
    • Journal Title

      Biochem. Biophys. Res. Comm.

      Volume: in press Issue: 2 Pages: 387-393

    • DOI

      10.1016/j.bbrc.2018.04.212

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elimination of a signal-sequence uncleaved form of defective HLA protein through BAG6.2017

    • Author(s)
      Yamamoto, K., Hayashishita, M., Minami, S., Suzuki, K., Hagiwara, T., Noguchi, A., and Kawahara, H.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-14975-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Reports

      Volume: 未定 Issue: 6 Pages: 842-857

    • DOI

      10.15252/embr.201541402

    • Related Report
      2016 Research-status 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 J.

      Volume: 283 Issue: 4 Pages: 662-677

    • DOI

      10.1111/febs.13618

    • Related Report
      2016 Research-status 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 Issue: 1-2 Pages: 1-12

    • DOI

      10.1007/s11010-015-2643-4

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 酸化ストレス存在下のBAG6複合体の役割2017

    • Author(s)
      横田直人、川原裕之
    • Organizer
      第40回日本分子生物学会 第90回日本生化学会 生命科学系合同年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミスローカライズしたGPIアンカー型タンパク質の代謝におけるBAG6の機能解析2017

    • Author(s)
      大野靖枝、横田直人、川原 裕之
    • Organizer
      第40回日本分子生物学会 第90回日本生化学会 生命科学系合同年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] BAG6依存的なRab-GTPase分解機構の解明2017

    • Author(s)
      高橋俊樹、川原 裕之
    • Organizer
      第40回日本分子生物学会 第90回日本生化学会 生命科学系合同年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリアタンパク質を標的とするBAG6新規機能の探索2017

    • Author(s)
      林下瑞希、川原 裕之
    • Organizer
      第40回日本分子生物学会 第90回日本生化学会 生命科学系合同年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] UBQLN4の基質認識機構の解明2017

    • Author(s)
      鈴木勘司、鈴木理滋、川原裕之
    • Organizer
      第40回日本分子生物学会 第90回日本生化学会 生命科学系合同年会
    • Related Report
      2017 Annual Research Report
  • [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
    • Organizer
      第39回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜,横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status 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
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター,仙台市
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status 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
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター,仙台市
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status 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
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター,仙台市
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status 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
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター,仙台市
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status 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.biol.se.tmu.ac.jp/labo.asp?ID=celche

    • Related Report
      2017 Annual Research Report
  • [Remarks] 首都大学東京理工学研究科生命科学専攻細胞生化学研究室ホームページ1

    • URL

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

    • Related Report
      2016 Research-status Report
  • [Remarks] 首都大学東京理工学研究科生命科学専攻細胞生化学研究室ホームページ2

    • URL

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

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-06-16  

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