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Elucidation of regulation mechanism of the endoplasmic reticulum membrane-bound transcription factor ATF6 and its role in the evolution of vertebrates

Research Project

Project/Area Number 26291040
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cell biology
Research InstitutionKyoto University

Principal Investigator

Mori Kazutoshi  京都大学, 理学(系)研究科(研究院), 教授 (70182194)

Co-Investigator(Renkei-kenkyūsha) OKADA Tetsuya  京都大学, 大学院理学研究科, 助教 (70378529)
ISHIKAWA Tokiro  京都大学, 大学院理学研究科, 助教 (70632545)
Research Collaborator TAKEDA Shunichi  京都大学, 大学院医学研究科, 教授
YAMAMOTO Takashi  広島大学, 大学院理学研究科, 教授
KATO Koichi  岡崎統合バイオサイエンスセンター, 教授
NINAGAWA Satoshi  京都大学, 大学院理学研究科, 博士研究員
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsタンパク質品質管理 / 小胞体 / 転写因子 / 分子シャペロン / 小胞体関連分解 / ゴルジ体 / エスコート / 進化 / 細部内情報伝達 / 小胞体ストレス / 小胞輸送 / 膜結合性転写因子 / エスコートタンパク質
Outline of Final Research Achievements

The endoplasmic reticulum (ER) membrane-bound transcription factor ATF6 is a protein with a short half-life of 2 h and constitutively subjected to glycan-dependent ER-associated degradation, although it functions as an ER stress sensor and transducer. I analyzed mannose trimming enzymes which are important for this degradation mechanism and discovered that the trimming of M9 to M8 is carried out by EDEM2 and that the trimming of M8 to M7 is carried out by EDEM1/3 (EDEM3 plays a major role). These results have completely renewed the previous model.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (15 results)

All 2016 2015 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Invited: 1 results) Remarks (3 results)

  • [Journal Article] PNGase sensitivity assay to study the folding status of proteins.2016

    • Author(s)
      S. Ninagawa and K. Mori
    • Journal Title

      Bio-protocol

      Volume: 6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Trypsin sensitivity assay to study the folding status of proteins.2016

    • Author(s)
      S. Ninagawa and K. Mori
    • Journal Title

      Bio-protocol

      Volume: 6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Forcible destruction of severely misfolded mammalian glycoproteins by the non-glycoprotein ERAD pathway.2015

    • Author(s)
      Ninagawa S, Okada T, Sumitomo Y, Horimoto S, Sugimoto T, Ishikawa T, Takeda S, Yamamoto T, Suzuki T, Kamiya Y, Kato K, Mori K.
    • Journal Title

      The Journal of Cellular Biology

      Volume: 211 Issue: 4 Pages: 775-784

    • DOI

      10.1083/jcb.201504109

    • NAID

      120005672576

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] EDEM2 Initiates Mammalian Glycoprotein ERAD by Catalyzing the First Mannose Trimming Step2014

    • Author(s)
      S. Ninagawa et al.
    • Journal Title

      Journal of Cell Biology

      Volume: 206 Pages: 347-356

    • NAID

      120005468381

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The unfolded protein response: to mammals and beyond2016

    • Author(s)
      K. Mori
    • Organizer
      Ada Doisy Lecture in Biochemistry
    • Place of Presentation
      University of Illinois, USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] The unfolded protein response: to mammals and beyond2016

    • Author(s)
      K. Mori
    • Organizer
      Special Lecture
    • Place of Presentation
      The National University of Ireland, Galway
    • Year and Date
      2016-11-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of UPR sensors: toward an understanding of physiological and pathological ER stress2016

    • Author(s)
      K. Mori
    • Organizer
      Nobel Forum "Unfolded proteins: from basic to bedside"
    • Place of Presentation
      Karolinska Institute, Stockholm, Sweden
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Protein quality control by the unfolded protein response2016

    • Author(s)
      K. Mori
    • Organizer
      2nd Mini-symposium on Cell Biology
    • Place of Presentation
      National Center for Cell Science, Pune, India
    • Year and Date
      2016-05-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] 小胞体ストレス応答によるタンパク質品質管理2015

    • Author(s)
      森 和俊
    • Organizer
      第10回臨床ストレス応答学会大会
    • Place of Presentation
      東京農工大
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] 小胞体ストレス応答によるタンパク質品質管理2015

    • Author(s)
      森 和俊
    • Organizer
      第24回日本Cell Death学会学術集会
    • Place of Presentation
      大阪大学会館(豊中キャンパス)
    • Year and Date
      2015-07-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 小胞体ストレス応答によるタンパク質品質管理2015

    • Author(s)
      森 和俊
    • Organizer
      第62回日本生化学会近畿支部例会
    • Place of Presentation
      立命館大 学草津キャンパス
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step2014

    • Author(s)
      森 和俊
    • Organizer
      第87回日本生化学会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] シビアな構造異常糖タンパク質が出現すると手順を踏まずに強制分解

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2015/151117_2.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] EDEM1/2/3ノックアウト細胞の解析結果をJCB reportにて発表

    • URL

      http://www.upr.biophys.kyoto-u.ac.jp/blog/edem1_2_3_jcb_report/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 構造異常糖タンパク質の分解に必須な糖鎖刈り込み機構を解明

    • URL

      http://www.kyoto-u.ac.jp/ja/research/research_results/2014/140902_1.html

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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