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Understanding mechanisms that regulate Runx complex function through C-terminus structures

Research Project

Project/Area Number 17H04090
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Taniuchi Ichiro  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (20284573)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords免疫細胞 / 細胞分化 / 転写因子 / Runx / 免疫細胞分化 / 遺伝子発現制御 / Runx転写因子 / T細胞分化 / アミノ酸置換変異 / T細胞 / 免疫学 / 獲得免疫 / タンパク構造 / アミノ酸点変異
Outline of Final Research Achievements

unx/Cbfb transcription factor complexes are known to play essential roles in regulating development of multiple types of cells. Our preliminary works showed that C-terminal end sequences of Runx and Cbfb2 are important for the function of Runx/Cbfb complexes. In this study, we focuses on the last Y residue in the Runx3 protein and replaced the Y with W, F or E residue. Analyses of these mutant lines suggested that the Y residue might be phosphorylated and this post-translational modification is quite essential for regulating the function of Runx protein.
As for the functional characterization of Cbfb2-specific C-terminal amino-acid sequences, proteomics approach and analyses of a new mutant strain lacking the above Cbfb2-specific C-terminal sequences failed to find Cbfb2-specific interacting partners and function, respectively. These finding suggest that RNA splicing at the Cbfb locus might contribute to regulate total amount of Cbfb protein.

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果からRunxタンパクの最後のY残基がRunxタンパクの機能、特に外部刺激に応答した遺伝子発現抑制と細胞周期制御に重要であることを強く示唆する結果を得た。免疫学領域では抗原受容体刺激後のリンパ球の選択機構の分子ネカニズムの解明は大きな課題であり、今回の成果はこの問題の解明に繋がる成果であると考えられる。

Report

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

    (23 results)

All 2020 2019 2018 Other

All Journal Article (14 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (7 results) (of which Int'l Joint Research: 6 results,  Invited: 7 results) Remarks (2 results)

  • [Journal Article] Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity2020

    • Author(s)
      Seo Wooseok、Shimizu Kanako、Kojo Satoshi、Okeke Arinze、Kohwi-Shigematsu Terumi、Fujii Shin-ichiro、Taniuchi Ichiro
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-020-15375-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Constitutive CD8 expression drives innate CD8+ T-cell differentiation via induction of iNKT2 cells2020

    • Author(s)
      Kojo Satoshi、Ohno-Oishi Michiko、Wada Hisashi、Nieke Sebastian、Seo Wooseok、Muroi Sawako、Taniuchi Ichiro
    • Journal Title

      Life Science Alliance

      Volume: 3 Issue: 2 Pages: 1-13

    • DOI

      10.26508/lsa.202000642

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Roles of RUNX Family Proteins in Development of Immune Cells.2020

    • Author(s)
      Seo Wooseok, Taniuchi Ichiro
    • Journal Title

      Molecular and Cells

      Volume: 43

    • Related Report
      2019 Annual Research Report
    • Open Access
  • [Journal Article] Essential functions of Runx/Cbfβ in gut conventional dendritic cells for priming Rorγt+ T cells2019

    • Author(s)
      Tenno Mari、Wong Alicia Yoke Wei、Ikegaya Mika、Miyauchi Eiji、Seo Wooseok、See Peter、Kato Tamotsu、Taida Takashi、Oishi-Ohno Michiko、Ohno Hiroshi、Yoshida Hideyuki、Ginhoux Florent、Taniuchi Ichiro
    • Journal Title

      Life Science Alliance

      Volume: 3 Issue: 1 Pages: 1-11

    • DOI

      10.26508/lsa.201900441

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ZBTB7B (ThPOK) IS REQUIRED FOR PATHOGENESIS OF CEREBRAL MALARIA AND PROTECTION AGAINST PULMONARY TUBERCULOSIS2019

    • Author(s)
      Kennedy James M.、Georges Anna、Bassenden Angelia V.、Vidal Silvia M.、Berghuis Albert M.、Taniuchi Ichiro、Majewski Jacek、Lathrop Mark、Behr Marcel A.、Langlais David、Gros Philippe
    • Journal Title

      Infection and Immunity

      Volume: 0 Issue: 2

    • DOI

      10.1128/iai.00845-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exhausted-like Group 2 Innate Lymphoid Cells in Chronic Allergic Inflammation2019

    • Author(s)
      Ebihara Takashi、Taniuchi Ichiro
    • Journal Title

      Trends in Immunology

      Volume: 40 Issue: 12 Pages: 1095-1104

    • DOI

      10.1016/j.it.2019.10.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians2019

    • Author(s)
      Hashimoto K, Kouno T, Ikawa T, Hayatsu N, Miyajima Y, Yabukami H, Terooatea T, Sasaki T, Suzuki T, Valentine M, Pascarella G, Minoda A, Taniuchi I, Arai Y, Hirose N, Carninci P
    • Journal Title

      PNAS

      Volume: 116 Issue: 48 Pages: 24242-24251

    • DOI

      10.1073/pnas.1907883116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Too much can be as bad as too little2019

    • Author(s)
      Seo Wooseok、Taniuchi Ichiro
    • Journal Title

      Nature Immunology

      Volume: 20 Issue: 10 Pages: 1262-1264

    • DOI

      10.1038/s41590-019-0498-7

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Anterior cleft palate due to Cbfb deficiency and its rescue by folic acid2019

    • Author(s)
      Sarper Safiye E.、Inubushi Toshihiro、Kurosaka Hiroshi、Ono Minagi Hitomi、Murata Yuka、Kuremoto Koh-ichi、Sakai Takayoshi、Taniuchi Ichiro、Yamashiro Takashi
    • Journal Title

      Disease Models & Mechanisms

      Volume: 12 Issue: 6 Pages: 038851-038851

    • DOI

      10.1242/dmm.038851

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation2019

    • Author(s)
      Miyamoto Chizuko、Kojo Satoshi、Yamashita Motoi、Moro Kazuyo、Lacaud Georges、Shiroguchi Katsuyuki、Taniuchi Ichiro、Ebihara Takashi
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 447-447

    • DOI

      10.1038/s41467-019-08365-0

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential Requirement of Cd8 Enhancers E8I and E8VI in Cytotoxic Lineage T Cells and in Intestinal Intraepithelial Lymphocytes2019

    • Author(s)
      Gulich Alexandra Franziska、Preglej Teresa、Hamminger Patricia、Alteneder Marlis、Tizian Caroline、Orola Maria Jonah、Muroi Sawako、Taniuchi Ichiro、Ellmeier Wilfried、Sakaguchi Shinya
    • Journal Title

      Frontiers in Immunology

      Volume: 10

    • DOI

      10.3389/fimmu.2019.00409

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Runx-dependent and silencer-independent repression of a maturation enhancer in the Cd4 gene2018

    • Author(s)
      Kojo Satoshi、Yasmin Nighat、Muroi Sawako、Tenno Mari、Taniuchi Ichiro
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 3593-3593

    • DOI

      10.1038/s41467-018-05803-3

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tle corepressors are differentially partitioned to instruct CD8+ T cell lineage choice and identity2018

    • Author(s)
      Xing Shaojun、Shao Peng、Li Fengyin、Zhao Xudong、Seo Wooseok、Wheat Justin C.、Ramasamy Selvi、Wang Jianfeng、Li Xiang、Peng Weiqun、Yu Shuyang、Liu Chengyu、Taniuchi Ichiro、Sweetser David A.、Xue Hai-Hui
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 215 Issue: 8 Pages: 2211-2226

    • DOI

      10.1084/jem.20171514

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CD4 Helper and CD8 Cytotoxic T Cell Differentiation2018

    • Author(s)
      Taniuchi Ichiro
    • Journal Title

      Annual Review of Immunology

      Volume: 36 Issue: 1 Pages: 579-601

    • DOI

      10.1146/annurev-immunol-042617-053411

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Roles of Bcl11 proteins During Thymocyte Differentiation2019

    • Author(s)
      谷内 一郎
    • Organizer
      IUIS 2019. 17th International Congress of Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Roles of Cbfβ in dendritic cells in priming Rorγt+ T cells2019

    • Author(s)
      谷内 一郎
    • Organizer
      RUNX 2019, 22nd International RUNX meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Heteromeric interference, a novel pathogenesis for human immunodeficiency2019

    • Author(s)
      谷内 一郎
    • Organizer
      ThymE: T cell and thymus biology(
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gene regulation by local and long-range chromatin loops during T cell development2019

    • Author(s)
      谷内 一郎
    • Organizer
      第42回分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Gene regulation by local and long-range chromatin loops during CD4/CD8 lineage choice2019

    • Author(s)
      Ichiro Taniuchi
    • Organizer
      The Keystone Symposia
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Unraveling pathogenesis of human primary immune deficiency by mouse models2018

    • Author(s)
      Ichiro Taniuchi
    • Organizer
      The 6th Kyoto Course on Bioinformatics for Genomic Medicine International Symposium on Disease Genomics
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of Dendritic Cell Development by Runx Factors2018

    • Author(s)
      Ichiro Taniuchi
    • Organizer
      The 1st International Symposium on NEO-SELF
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 免疫転写制御研究チーム

    • URL

      https://www.riken.jp/research/labs/ims/transcript_reg/

    • Related Report
      2019 Annual Research Report
  • [Remarks] がん免疫におけるケモカインCCL5発現抑制機構の解明

    • URL

      https://www.riken.jp/press/2020/20200326_3/index.html

    • Related Report
      2019 Annual Research Report

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

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