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Transciptional regulation through the autophay

Research Project

Project/Area Number 17K07285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionOsaka University

Principal Investigator

Ogawa Hidesato  大阪大学, 生命機能研究科, 特任准教授(常勤) (20370132)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords転写制御 / クロマチン構造変換 / 転写複合体 / オートファジー / タンパク質複合体 / 転写因子 / 核内複合体 / 翻訳後修飾 / 遺伝子発現制御機構 / 転写
Outline of Final Research Achievements

The extracellular signal tightly regulates transcriptional activity to maintain cell differentiation and homeostasis. Several lines of evidence clearly showed that protein degradation mediated by the autophagy system is a vitally important means of regulation for transcriptional processes. In this study, we attempted to elucidate a novel molecular mechanism of autophagy-mediated transcriptional regulation in response to extracellular signals by analyzing the nuclear function of the selective autophagy receptor p62. To gain insight into the molecular mechanism of p62, we attempted to purify the nuclear p62 complex and identify its components. Interestingly, the complex contained some senescence and oncogenic proteins. Furthermore, Adenovirus protein tightly bound to this complex and colocalized ARIP4. These data strongly suggested that p62 acts as a sensing factor for virus infection and important for the cellular response through transcriptional regulation.

Academic Significance and Societal Importance of the Research Achievements

本研究では,細胞質タンパク質の分解制御にのみ関わると考えられてきたオートファジー機構が核内において遺伝子発現制御を介した細胞の老化やガンの発生に密接に関与していることを示した。更に興味深いことに,ヒト感染症疾患の原因となるアデノウイルスの侵入は,ウイルスタンパクがこの分子機構を撹乱させることで自らの増殖と細胞の状態をコントロールしている可能性があり,この分子機構がウイルスなど異物排除機構の制御に極めて重要なことを裏付けている。本成果は未だ多くが解明されていないガンの発生制御機構やウイルスの感染防御機構を明らかにする上で極めて重要な証拠となるものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Instit of the Polish Academy of Sciences(ポーランド)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Possible Mechanisms for Maintenance and Regression of Corpus Luteum Through the Ubiquitin- Proteasome and Autophagy System Regulated by Transcriptional Factors2019

    • Author(s)
      Teeli Aamir S.、Leszczynski Pawel、Krishnaswamy Narayanan、Ogawa Hidesato、Tsuchiya Megumi、Smiech Magdalena、Skarzynski Dariusz、Taniguchi Hiroaki
    • Journal Title

      Frontiers in Endocrinology

      Volume: 10

    • DOI

      10.3389/fendo.2019.00748

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids2018

    • Author(s)
      Takashi Baba, Hiroyuki Otake, Miki Inoue, Tetsuya Sato, Yasuhiro Ishihara, Ju-Yeon Moon, Megumi Tsuchiya, Kanako Miyabayashi, Hidesato Ogawa, Yuichi Shima, Lixiang Wang, Ryuichiro Sato, Takeshi Yamazaki, Mikita Suyama, Masatoshi Nomura, Man Ho Choi, Yasuyuki Ohkawa & Ken-ichirou Morohashi
    • Journal Title

      Communications Biology

      Volume: 1 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s42003-018-0020-z

    • NAID

      120006799378

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Shelterin promotes tethering of late replication origins to telomeres for replication‐timing control2018

    • Author(s)
      Ogawa Shiho、Kido Sayuri、Handa Tetsuya、Ogawa Hidesato、Asakawa Haruhiko、Takahashi Tatsuro S、Nakagawa Takuro、Hiraoka Yasushi、Masukata Hisao
    • Journal Title

      The EMBO Journal

      Volume: 37 Issue: 15 Pages: 15-15

    • DOI

      10.15252/embj.201898997

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy2018

    • Author(s)
      Tsuchiya Megumi、Ogawa Hidesato、Koujin Takako、Mori Chie、Osakada Hiroko、Kobayashi Shouhei、Hiraoka Yasushi、Haraguchi Tokuko
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 3 Pages: 470-480

    • DOI

      10.1002/2211-5463.12385

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ess2 bridges transcriptional regulators and spliceosomal complexes via distinct interacting domains2018

    • Author(s)
      Ichiro Takada, Megumi Tsuchiya, Kaori Yanaka, Shinya, Hidano, Sayuri Takahashi, Takashi Kobayashi, Hidesato Ogawa, Sinichi Nakagawa, Makoto Makishima
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497 Issue: 2 Pages: 597-604

    • DOI

      10.1016/j.bbrc.2018.02.110

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Regulation of autophagy receptor p62/SQSTM1 enhances the efficiency of gene delivery in mammalian cells2019

    • Author(s)
      Hidesato Ogawa
    • Organizer
      Lecture of Institute of Genetics and Animal Breeding of the Polish Academy of Sciences
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 選択的オートファジー機構を介した細胞自己防衛機構の解明2019

    • Author(s)
      小川英知
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 選択的オートファジー機構を介した細胞自己防衛機構の解明2019

    • Author(s)
      小川 英知、土屋 惠、渡邊賢人,荒神 尚子、森 知栄、小林 昇平、平岡 泰、原口 徳子
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Depletion of autophagy receptor p62/SQSTM1 enhances the efficiency of gene delivery in mammalian cells2018

    • Author(s)
      Hidesato Ogawa, Megumi Tsuchiya, Takako Koujin, Chie Mori, Hiroko Osakada, Kento Watanabe, Shouhei Kobayashi, Yasushi Hiraoka, Tokuko Haraguchi
    • Organizer
      第70回細胞生物第51回発生生物合同大会
    • Related Report
      2018 Research-status Report
  • [Presentation] オートファジーレセプターp62/SQSTM1 を標的とした効果的な遺伝子導入法の確立2018

    • Author(s)
      土屋 惠, 小川英知, 渡邊 賢人,荒神 尚子, 小林 昇平, 森 知栄, 小坂田 裕子, 平岡 泰, 原口 徳子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Depletion of autophagy receptor p62/SQSTM1 enhances the efficiency of gene delivery in mammalian cells2017

    • Author(s)
      Hidesato Ogawa, Megumi Tsuchiya, Takako Koujin, Shouhei Kobayashi, Chie Mori, Yasushi Hiraoka, Tokuko Haraguchi
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Depletion of autophagy receptor p62/SQSTM1 enhances the efficiency of gene delivery in mammalian cells2017

    • Author(s)
      Megumi Tsuchiya, Hidesato Ogawa, Takako Koujin, Shouhei Kobayashi, Chie Mori, Hiroko Osakada, Yasushi Hiraoka, Tokuko Haraguchi
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Remarks] 大阪大学生命機能研究科細胞核ダイナミクス研究室ホームページ

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/hiraoka/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 大阪大学大学院生命機能研究科細胞核ダイナミクス研究室ホームページ

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/hiraoka/index.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 大阪大学大学院 生命機能研究科 細胞ネットワーク講座 研究室ホームページ

    • URL

      http://www.fbs.osaka-u.ac.jp/labs/hiraoka/member.html

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 2種類のTBK1/IKKe阻害剤を利用した核酸導入2020

    • Inventor(s)
      小川英知,土屋惠,渡邊賢人,平岡泰,原口徳子
    • Industrial Property Rights Holder
      小川英知,土屋惠,渡邊賢人,平岡泰,原口徳子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-000088
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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