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Elucidation of the mechanism for the proteasome assembly regulated by

Research Project

Project/Area Number 16K07342
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionThe University of Tokyo

Principal Investigator

Yashiroda Hideki  東京大学, 大学院薬学系研究科(薬学部), 准教授 (20311425)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプロテアソーム / リボソーム / 複合体形成 / タンパク質分解 / タンパク質合成 / 出芽酵母
Outline of Final Research Achievements

TIF6 was isolated as a gene related to the ubiquitin-proteasome system (UPS) in S. cerevisiae. TIF6 (translation initiation factor 6) is an essential gene, and encodes one of the chaperone proteins involved in the biogenesis of the 60S ribosome. DAmP (decreased abundance by mRNA perturbation) mutant cells of Tif6 showed three phenotypes, all of which indicate the relation between Tif6 and the UPS. 1) tif6-DAmP cells are sensitive to the amino acid analogs. 2) The model substrates of the 26S proteasome are not efficiently degraded in the tif6-DAmP mutant. 3) Double mutations of TIF6 and the proteasome genes cause synthetic growth defects. Tif6 is a highly conserved among eukaryotes, and its human ortholog is eIF6 (>70% identity). Thus, we next investigated the relation between eIF6 and the UPS. Knockdown of eIF6 led to retardation of the assembly of proteasomes, and yeast two-hybrid assays indicated that eIF6 interacts with some proteasome subunits.

Academic Significance and Societal Importance of the Research Achievements

細胞内における選択的なタンパク質分解のためのマシナリーであるプロテアソームとタンパク質合成のためのマシナリーであるリボソームとがTif6/eIF6を介して関連している可能性を示唆した。Tif6/eIF6は60Sリボソームの形成に関わるシャペロンであると同時に、80Sリボソーム形成においてチェックポイント機能を果たす分子でもあることが知られていた。Tif6/eIF6の発現減弱細胞はさらにプロテアソーム形成にも異常を示し、またプロテアソームサブユニットとも相互作用することが今回明らかとなり、タンパク質合成とタンパク質分解が協調している可能性を示した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] PAC1-PAC2 proteasome assembly chaperone retains the core α4-α7 assembly intermediates in the cytoplasm.2018

    • Author(s)
      Wu W, Sahara K, Hirayama S, Zhao X, Watanabe A, Hamazaki J, Yashiroda H, Murata S.
    • Journal Title

      Gene to Cells

      Volume: 10 Issue: 10 Pages: 839-848

    • DOI

      10.1111/gtc.12631

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] リボソームタンパク質の脱ユビキチン化による翻訳制御機構の解明2019

    • Author(s)
      竹原由香、八代田英樹、村田茂穂
    • Organizer
      「ケモユビキチン」第1回班会議・第2回ユビキチン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 出芽酵母を用いた哺乳類のプロテアソーム20S core particle再構成2018

    • Author(s)
      石原慧、松崎哲郎、八代田英樹、村田茂穂
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Functional analysis of UBL-UBA domain containing yeast protease Ddi1 and its human ortholog DDI22018

    • Author(s)
      Yan Wang, Noritaka Ohigashi, Hideki Yashiroda, Shigeo Murata
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HECT型ユビキチンリガーゼHul5は変異型SOD1の核外排出に関与する2017

    • Author(s)
      大東宣貴、平山尚志郎、○八代田英樹、村田茂穂
    • Organizer
      酵母遺伝学フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] 出芽酵母脱ユビキチン化酵素 Otu2と Ubp3のリボソームに対する重複した機能の可能性2017

    • Author(s)
      ○竹原由香、八代田英樹、村田茂穂
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 26S プロテアソームと20S core particle との量比は、グルコース濃度によって制御される2017

    • Author(s)
      ○池浦隆真、八代田英樹、村田茂穂
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Exploring modulators of the toxicity by amyloidogenic proteins2017

    • Author(s)
      ○Xiaochen Cai, Tetsuo Matsuzaki, Shoshiro Hirayama, Hideki Yashiroda, Shigeo Murata
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Eukaryotic initiation factor 6 (eIF6) is involved in the assembly of the proteasome core particle2016

    • Author(s)
      Tetsuo Matsuzaki, Hideki Yahiroda, Shigeo Murata
    • Organizer
      Cold Spring Harbor Asia Symposium "Ubiquitin Family, Autophagy & Diseases"
    • Place of Presentation
      Suzhou (China)
    • Year and Date
      2016-04-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Eukaryotic initiation factor 6 (eIF6) is involved in the assembly of the proteasome core particle2016

    • Author(s)
      Tetsuo Matsuzaki, Hideki Yahiroda, Shigeo Murata
    • Organizer
      第16回東京大学生命科学シンポジウム
    • Place of Presentation
      東京大学駒場キャンパス 21 Komcee (東京都目黒区)
    • Related Report
      2016 Research-status Report
  • [Presentation] 翻訳開始因子eIF6/Tif6のプロテアソーム形成への関与2016

    • Author(s)
      八代田英樹、松崎哲郎、村田茂穂
    • Organizer
      第191回酵母細胞研究会例会
    • Place of Presentation
      キリンビール(株)横浜工場総合棟ホール(神奈川県横浜市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 東京大学薬学部蛋白質代謝学教室

    • URL

      http://www.f.u-tokyo.ac.jp/~tanpaku/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院薬学系研究科蛋白質代謝学教室ホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~tanpaku/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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