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Regulation of signal transduction by TRIM family ubiquitin ligases

Research Project

Project/Area Number 21H02674
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionHokkaido University

Principal Investigator

Hatakeyama Shigetsugu  北海道大学, 医学研究院, 教授 (70294973)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywordsユビキチン / TRIMタンパク質 / シグナル伝達 / がん化 / 細胞内シグナル伝達 / 質量分析 / がん
Outline of Research at the Start

本研究における「問い」は、ユビキチン化システムにおいて多彩に進化し、遺伝子数を増加させてきたTRIMファミリーが、ヒトの生体機能とどのように連関して進化してきたのかである。そのため、細胞内シグナル伝達などの哺乳類で重要な細胞機能とTRIMファミリーの関係を俯瞰的かつ網羅的に解明することを試みる。最終的には、TRIMファミリーによる翻訳後修飾(特にユビキチン化)の生理機能および疾患との関連の解明を目指し、感染症、自己免疫疾患、がん化、細胞分化、個体発生、神経変性疾患などにおける総合的理解を深める。

Outline of Final Research Achievements

Recently, the importance of TRIM family ubiquitin ligases in intracellular signal transduction related to immune responses and cancerization has been clarified. In particular, TRIM family ubiquitin ligases have been shown to be involved not only in cell proliferation but also in signal transduction systems that control cell differentiation processes and autophagy regulation, and have recently attracted attention in many fields of intracellular signal transduction systems. In this application, we comprehensively analyzed the intracellular network system centered on TRIM family ubiquitin ligases using comprehensive knockdown screening and proteomics methods specific to ubiquitination.

Academic Significance and Societal Importance of the Research Achievements

これまでは各TRIMタンパク質の機能が個別に報告されてきたが、本申請研究では全TRIMタンパク質のsiRNAやプロテオミクス的解析等を使用することで、さまざまな細胞内シグナルを網羅的に解析し、TRIMファミリー全体のシステム構造の解明を進めた。今後、TRIMファミリーによる翻訳後修飾(特にユビキチン化)の生理機能および疾患との関連の解明という点で、感染症、自己免疫疾患、がん化、細胞分化、個体発生、神経変性疾患など、医学における総合的理解に貢献する可能性が高い。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (11 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] FBXO11 constitutes a major negative regulator of MHC class II through ubiquitin-dependent proteasomal degradation of CIITA2023

    • Author(s)
      Kasuga Yusuke、Ouda Ryota、Watanabe Masashi、Sun Xin、Kimura Miki、Hatakeyama Shigetsugu、Kobayashi Koichi S.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 24

    • DOI

      10.1073/pnas.2218955120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sez6l2 autoimmunity in a large cohort study2023

    • Author(s)
      Abe M, Yaguchi H, Kudo A, Nagai A, Shirai S, Takahashi-Iwata I, Matsushima M, Nakamura N, Isahaya K, Yamano Y, Ashida S, Kasai T, Tanaka K, Watanabe M, Kondo T, Takahashi H, Hatakeyama S, Takekoshi A, Kimura A, Shimohata T, Yabe I.
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 94 Issue: 8 Pages: 667-668

    • DOI

      10.1136/jnnp-2022-330194

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma2023

    • Author(s)
      Kimura S、Suzuki M、Nakamaru Y、Kano S、Watanabe M、Honma A、Nakazono A、Tsushima N、Hatakeyama S、Homma A
    • Journal Title

      Rhinology Journal

      Volume: - Issue: 0 Pages: 0-0

    • DOI

      10.4193/rhin22.405

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM22 negatively regulates MHC-II expression2022

    • Author(s)
      Inoue Ayano、Watanabe Masashi、Kondo Takeshi、Hirano Satoshi、Hatakeyama Shigetsugu
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1869 Issue: 10 Pages: 119318-119318

    • DOI

      10.1016/j.bbamcr.2022.119318

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Curcumin partly prevents ISG15 activation via ubiquitin-activating enzyme E1-like protein and decreases ISGylation2022

    • Author(s)
      Oki Nodoka、Yamada Shino、Tanaka Tamaki、Fukui Hiromi、Hatakeyama Shigetsugu、Okumura Fumihiko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 625 Pages: 94-101

    • DOI

      10.1016/j.bbrc.2022.08.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of FAM83H promotes cell migration and invasion in cutaneous squamous cell carcinoma via impaired keratin distribution2021

    • Author(s)
      Tokuchi Keiko、Kitamura Shinya、Maeda Takuya、Watanabe Masashi、Hatakeyama Shigetsugu、Kano Satoshi、Tanaka Shinya、Ujiie Hideyuki、Yanagi Teruki
    • Journal Title

      Journal of Dermatological Science

      Volume: 104 Issue: 2 Pages: 112-121

    • DOI

      10.1016/j.jdermsci.2021.09.007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells2021

    • Author(s)
      Nakazono Akira、Nakamaru Yuji、Ramezanpour Mahnaz、Kondo Takeshi、Watanabe Masashi、Hatakeyama Shigetsugu、Kimura Shogo、Honma Aya、Wormald P. J.、Vreugde Sarah、Suzuki Masanobu、Homma Akihiro
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 11 Pages: 655666-655666

    • DOI

      10.3389/fcimb.2021.655666

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases2021

    • Author(s)
      Suzuki Masanobu、Suzuki Takayoshi、Watanabe Masashi、Hatakeyama Shigetsugu、Kimura Shogo、Nakazono Akira、Honma Aya、Nakamaru Yuji、Vreugde Sarah、Homma Akihiro
    • Journal Title

      Allergology International

      Volume: 70 Issue: 2 Pages: 190-200

    • DOI

      10.1016/j.alit.2020.09.007

    • NAID

      130008024307

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] がん遺伝子産物PPM1Dのタンパク質分解機構2023

    • Author(s)
      渡部昌, 高橋正樹, 畠山鎮次
    • Organizer
      日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 自己免疫性小脳失調症に対する免疫沈降法と質量分析法を用いた網羅的自己抗体測定方法の開発2023

    • Author(s)
      工藤 彰彦, 矢口 裕章, 渡部 昌, 上床 尚, 白井 慎一, 岩田 育子, 松島 理明, 高橋 秀尚, 畠山 鎮次, 矢部 一郎
    • Organizer
      日本神経免疫学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] TRIMタンパク質の機能と多様な疾患への関与2022

    • Author(s)
      畠山鎮次
    • Organizer
      ATAGO Respiratory Expert Seminar
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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