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Comprehensive analysis of kinases and phosphatases that regulate the endoplasmic reticulum stress response in the budding yeast

Research Project

Project/Area Number 19K06632
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Mizuno Tomoaki  筑波大学, 医学医療系, 准教授 (80529032)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小胞体ストレス / キナーゼ / ホスファターゼ / オートファジー / 遺伝子発現制御 / 転写因子
Outline of Research at the Start

ストレス応答においては、複数のシグナル伝達経路が、各々に特有のタイムコースで活性化・不活性化することで、適切な細胞応答を誘導する。本研究では、出芽酵母全キナーゼ・ホスファターゼ変異株作製とその小胞体ストレス感受性検定をおこなうことで、小胞体ストレス応答に機能するキナーゼ・ホスファターゼを網羅的に抽出する。そして、各因子の作用機構・制御機構を明らかにする。本研究は、真核生物の最も単純なモデル系である出芽酵母の特長を生かし、高等真核生物では実現が難しい網羅的かつ高精度な解析をおこなうことで、タンパク質リン酸化制御の側面から、小胞体ストレス応答の惹起から終結までの全体像の理解に貢献していく。

Outline of Final Research Achievements

To comprehensively extract kinases and phosphatases that function in the endoplasmic reticulum (ER) stress response in budding yeast, we generated gene-deficient or loss-of-function mutant strains for all 123 kinases and 35 phosphatases and examined their susceptibility to ER stress. As a result, we found that 34 mutants were sensitive to ER stress and 16 mutants were resistant to ER stress. We also analyzed the regulatory mechanism of ER stress-induced ER-selective autophagy (ER-phagy) and found that the expression of ER-phagy receptor Atg39 is positively regulated by Snf1 AMP-activated kinase and negatively regulated by protein kinase A.

Academic Significance and Societal Importance of the Research Achievements

小胞体ストレス応答は細胞小器官である小胞体に不良タンパク質が蓄積した際に誘導される生体防御機構であり、酵母からヒトに至る真核生物で保存されている。ヒトにおいては、小胞体ストレス応答の破綻は糖尿病・神経変性疾患・がんなど多様な疾病の発病と進行に関与している。本研究では、細胞応答の中核を担うタンパク質リン酸化酵素・脱リン酸化酵素の中から小胞体ストレス応答に関与する因子を抽出できたこと、タンパク質リン酸化酵素群を介した小胞体分解機構を明らかにしており、小胞体ストレス応答に起因した疾病の予防と治療に貢献する可能性を秘めている。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (1 results)

  • [Journal Article] Msn2/4 transcription factors positively regulate expression of Atg39 ER-phagy receptor2021

    • Author(s)
      Mizuno Tomoaki、Irie Kenji
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 11919-11919

    • DOI

      10.1038/s41598-021-91480-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pbp1, the yeast ortholog of human Ataxin-2, functions in the cell growth on non-fermentable carbon sources.2021

    • Author(s)
      Tuong Vi DT, Fujii S, Valderrama AL, Ito A, Matsuura E, Nishihata A, Irie K, Suda Y, Mizuno T, Irie K.
    • Journal Title

      PLOS ONE

      Volume: in press Issue: 5 Pages: e0251456-e0251456

    • DOI

      10.1371/journal.pone.0251456

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pan2-Pan3 complex, together with Ccr4-Not complex, has a role in the cell growth on non-fermentable carbon sources2021

    • Author(s)
      Fujii Shiori、Duy Duong Long、Valderrama Arvin Lapiz、Takeuchi Risa、Matsuura Eri、Ito Ayaka、Irie Kaoru、Suda Yasuyuki、Mizuno Tomoaki、Irie Kenji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 570 Pages: 125-130

    • DOI

      10.1016/j.bbrc.2021.07.007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pbp1 mediates the aberrant expression of genes involved in growth defect of ccr4 and pop2 mutants in yeast Saccharomyces cerevisiae2021

    • Author(s)
      Valderrama Arvin Lapiz、Fujii Shiori、Duy Duong Long、Irie Kaoru、Mizuno Tomoaki、Suda Yasuyuki、Irie Kenji
    • Journal Title

      Genes to Cells

      Volume: - Issue: 6 Pages: 381-398

    • DOI

      10.1111/gtc.12846

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The eIF4E-binding protein Eap1 has similar but independent roles in cell growth and gene expression with the cytoplasmic deadenylase Ccr42021

    • Author(s)
      Higuchi Yudai、Fujii Shiori、Valderrama Arvin Lapiz、Irie Kaoru、Suda Yasuyuki、Mizuno Tomoaki、Irie Kenji
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: - Issue: 6 Pages: 1452-1459

    • DOI

      10.1093/bbb/zbab056

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Snf1 AMPK positively regulates ER-phagy via expression control of Atg39 autophagy receptor in yeast ER stress response2020

    • Author(s)
      Mizuno Tomoaki、Muroi Kei、Irie Kenji
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 9 Pages: e1009053-e1009053

    • DOI

      10.1371/journal.pgen.1009053

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pop2 Phosphorylation at S39 Contributes to the Glucose Repression of Stress Response Genes, HSP12 and HSP262019

    • Author(s)
      Lien PTK, Viet NTM, Mizuno T, Suda Y, Irie K.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 4 Pages: e0215064-e0215064

    • DOI

      10.1371/journal.pone.0215064

    • NAID

      120007133492

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] RGG-motifタンパク質による小胞体ストレス応答の制御2021

    • Author(s)
      遠藤雅、入江賢児、水野智亮
    • Organizer
      酵母遺伝学フォーラム 第54回研究報告会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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