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Functional analysis of O-GlcNAc glycan to determine the properties of EGFR ligands

Research Project

Project/Area Number 19K16073
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionNagoya University

Principal Investigator

Ogawa Mitsutaka  名古屋大学, 医学系研究科, 助教 (70727429)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords糖鎖 / EGFR / EGF受容体 / 運命決定 / EGFリガンド / Notch / リガンド / EGFR シグナル / O-GlcNAc / 糖鎖修飾
Outline of Research at the Start

本研究は、O-GlcNAc glycan が Notch シグナルだけではなく、EGFR シグナルも制御する糖鎖であることを実証することを目的とする。O-GlcNAc glycan は、Notch1 などの EGF ドメインに生じる非典型的な糖鎖修飾である。O-GlcNAc glycan の異常は Notch シグナルの破綻を引き起こし、その結果、先天性疾患や異常な血管新生の原因となる。本研究で O-GlcNAc glycan の多様性がEGFR シグナルを制御することが実証できれば、糖鎖多様性の基本原理を初めて明確に証明することになる。

Outline of Final Research Achievements

This is the first study in the world to demonstrate that O-GlcNAc glycan may be a glycan that regulates not only Notch signaling but also EGFR signaling. If the diversity of O-GlcNAc glycan found in this study can be demonstrated to regulate EGFR signaling, it will lead to a new understanding of the biological significance of O-GlcNAc glycan.

Academic Significance and Societal Importance of the Research Achievements

本研究では、癌の悪性化や個体発生に重要な機能をもつEGFRシグナルを制御する新しい糖鎖修飾を見出すことができた。このことは、癌の成り立ちや生物の成り立ちを理解する上で、非常に重要な発見であり、創薬研究への応用や再生医療分野への貢献が期待でき、学術的にも社会的にも非常に意義がある研究成果である。

Report

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

    (33 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (27 results) (of which Int'l Joint Research: 5 results) Book (1 results)

  • [Journal Article] Glycoproteomics of NOTCH1 EGF repeat fragments overexpressed with different glycosyltransferases in HEK293T cells reveals insights into O-GlcNAcylation of NOTCH12022

    • Author(s)
      Tsukamoto Yohei、Ogawa Mitsutaka、Yogi Kentarou、Tashima Yuko、Takeuchi Hideyuki、Okajima Tetsuya
    • Journal Title

      Glycobiology

      Volume: N/A Issue: 7 Pages: 616-628

    • DOI

      10.1093/glycob/cwac015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bioinformatics and Functional Analyses Implicate Potential Roles for EOGT and L-fringe in Pancreatic Cancers2021

    • Author(s)
      Barua Rashu、Mizuno Kazuyuki、Tashima Yuko、Ogawa Mitsutaka、Takeuchi Hideyuki、Taguchi Ayumu、Okajima Tetsuya
    • Journal Title

      Molecules

      Volume: 26 Issue: 4 Pages: 882-882

    • DOI

      10.3390/molecules26040882

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of extracellular O-GlcNAc to the stability of folded epidermal growth factor-like domains and Notch1 trafficking2020

    • Author(s)
      Ogawa M, Tashima Y, Sakaguchi Y, Takeuchi H and Okajima T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 526 Issue: 1 Pages: 184-190

    • DOI

      10.1016/j.bbrc.2020.03.066

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] N-Glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization2020

    • Author(s)
      Alam Sayad Md. Didarul、Tsukamoto Yohei、Ogawa Mitsutaka、Senoo Yuya、Ikeda Kazutaka、Tashima Yuko、Takeuchi Hideyuki、Okajima Tetsuya
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 25 Pages: 8560-8574

    • DOI

      10.1074/jbc.ra119.012280

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycoproteomic analysis identifies cryptdin-related sequence 1 as O-glycosylated protein modified with α1,2-fucose in the small intestine2020

    • Author(s)
      Hashiguchi Hiroki、Tsukamoto Yohei、Ogawa Mitsutaka、Tashima Yuko、Takeuchi Hideyuki、Nakamura Masanao、Kawashima Hiroki、Fujishiro Mitsuhiro、Okajima Tetsuya
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 695 Pages: 108653-108653

    • DOI

      10.1016/j.abb.2020.108653

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 3’-Sialyllactose on Notch: NOTCH1 functions as a scafold of O-linked, 3′-sialyllactosylated glycans2020

    • Author(s)
      Yohei Tsukamoto, Kazuhiro Aoki, Yoshiki Narimatsu, Yusuke Urata, Wataru Saiki, Mitsutaka Ogawa, Henrik Clausen, Michael Tiemeyer, Tetsuya Okajima, Hideyuki Takeuchi
    • Organizer
      Virtual 2020 Society of Glycobiology Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive O-GlcNAc glycoproteomics on NOTCH1 EGF repeats refined the sequons for O-GlcNAcylation and uncovered unique Lewis X epitopes in mammals2020

    • Author(s)
      Mitsutaka Ogawa, Yohei Tsukamoto, Kenntarou Yogi, Yuya Senoo, Kazutaka Ikeda, Hideyuki Takeuchi, Tetsuya Okajima
    • Organizer
      Virtual 2020 Society of Glycobiology Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] N-glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization.2020

    • Author(s)
      Sayad Md. Didarul Alam, Yohei Tsukamoto, Mitsutaka Ogawa, Yuya Senoo, Kazutaka Ikeda, Yuko Tashima, Hideyuki Takeuchi, Tetsuya Okajima
    • Organizer
      Virtual 2020 Society of Glycobiology Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血液凝固第XII因子の活性化抑制における糖鎖修飾の役割2020

    • Author(s)
      中村 澄香, 小川 光貴, 竹内 英之, 岡島 徹也, 有森 貴夫, 高木 淳一, 相川 京子
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 細胞外O-GlcNAc修飾はEGFドメインの安定性とNotch1のトラフィッキングへの寄与する2020

    • Author(s)
      小川 光貴, 田嶌 優子, 坂口 大和, 竹内 英之, 岡島 徹也
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Contribution of extracellular O-GlcNAc to the stability of folded epidermal growth factor-like domains and Notch1 trafficking2020

    • Author(s)
      Ogawa Mitsutaka、Tashima Yuko、Sakaguchi Yamato、Takeuchi Hideyuki、Okajima Tetsuya
    • Organizer
      GlycoT2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] N-glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization.2020

    • Author(s)
      Sayad Md. Didarul Alam, Yohei Tsukamoto, Mitsutaka Ogawa, Yuya Senoo, Kazutaka Ikeda, Yuko Tashima, Hideyuki Takeuchi, Tetsuya Okajima
    • Organizer
      GlycoT2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] N-glycans on EGF domain-specific O-GlcNAc transferase facilitate protein maturation and peripheral endoplasmic reticulum localization2020

    • Author(s)
      Sayad Md. Didarul Alam, Yohei Tsukamoto, Mitsutaka Ogawa, Yuya Senoo, Kazutaka Ikeda, Yuko Tashima, Hideyuki Takeuchi, Tetsuya Okajima
    • Organizer
      第 84回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] Regulation of transport of Delta-like1 homolog from endoplasmic reticulum mediated by O-glycans2020

    • Author(s)
      Yuko Tashima, Wakako Goto, YuyaSenoo, Yohei Tsukamoto, Kazutaka Ikeda, Mitsutaka Ogawa, Hideyuki Takeuchi, Tetsuya Okajima
    • Organizer
      第 84回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 細胞外 O-GlcNAc 修飾は EGF ドメインの安定性と Notch1 のトラフィッキングへの寄与する2020

    • Author(s)
      小川光貴, 田嶌優子, 坂口大和, 竹内英之, 岡島徹也
    • Organizer
      第 84回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] Notch 受容体上の O-結合型糖鎖修飾の質量分析計を用いた網羅的解析2020

    • Author(s)
      塚本庸平, 青木一弘, 成松由規, 浦田悠輔, 齊木颯, 小川光貴, Tiemeyer, Henrik Clausen, 岡島徹也, 竹内英之
    • Organizer
      第 84回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of fucose-containing novel O-GlcNAc glycan2019

    • Author(s)
      Mitsutaka Ogawa,Kentarou Yogi,Yuya Senoo,Kazutaka Ikeda,Hideyuki Takeuchi,Tetsuya Okajima
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch1 受容体上のO-GlcNAc glycan は細胞外環境に応答する2019

    • Author(s)
      与儀賢太朗,小川光貴,妹尾勇弥,池田和貴,竹内英之,岡島徹也
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Delta-like1 homologのO型糖鎖修飾による細胞膜発現制御機構の解析2019

    • Author(s)
      田嶌優子,後藤和佳子,妹尾勇弥,塚本 庸平,池田和貴,小川光貴,竹内英之,岡島徹也
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch受容体糖鎖による生体機能の精密制御機構の理解を目指したグライコプロテオミクス研究2019

    • Author(s)
      岡島徹也,小川光貴,竹内英之
    • Organizer
      第9回 名古屋大学医学系研究科・生理学研究所合同シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch1 受容体上のO-GlcNAc glycan は細胞外環境に応答する2019

    • Author(s)
      小川光貴,与儀賢太朗,妹尾勇弥,池田和貴,竹内英之,岡島徹也
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch 受容体上の O- 結合型糖鎖修飾の質量分析計を用いた網羅的解析2019

    • Author(s)
      塚本庸平,妹尾勇弥,浦田悠輔,齊木颯,小川光貴,池田和貴,竹内英之,岡島徹也
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effect of N-glycan on ER localized O-GlcNAc transferase (EOGT) and O-GlcNAcylation on Notch1 extracellular domains2019

    • Author(s)
      Sayad Md. Didarul Alam,Mitsutaka Ogawa,Yuko Tashima,Hideyuki Takeuchi,Tetsuya Okajima
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Delta-like 1 homolog の細胞膜発現の制御機構の解析2019

    • Author(s)
      田嶌優子,後藤和佳子,妹尾勇弥,塚本庸平,池田和貴,小川光貴,竹内英之,岡島徹也
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血液凝固第 XII 因子の活性化における EGF 様ドメインの O-結合型糖鎖修飾 の役割2019

    • Author(s)
      中村澄香,小川光貴,竹内英之,岡島徹也,有森貴夫,高木淳一,相川京子
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 構造学的なアプローチによる 細胞外 O-GlcNAc 修飾の分子機能解析2019

    • Author(s)
      小川光貴,矢木宏和,田嶌優子,妹尾勇弥,池田和貴,加藤晃一,竹内英之,岡島徹也
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch 受容体上の O-結合型糖鎖修飾の質量分析計を用いた網羅的解析2019

    • Author(s)
      塚本庸平,浦田悠輔,齊木颯,小川光貴,竹内英之,岡島徹也
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effect of N-glycan on EOGT and O-GlcNAcylation on Notch extracellular domains2019

    • Author(s)
      Sayad Md. Didarul Alam,Mitsutaka Ogawa,Hideyuki Takeuchi,Tetsuya Okajima
    • Organizer
      第83回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch1 受容体上のO-GlcNAc glycan は細胞外環境に応答する2019

    • Author(s)
      与儀賢太朗,小川光貴,妹尾勇弥,池田和貴,竹内英之,岡島徹也
    • Organizer
      第83回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] O-GlcNAc は Notch 受容体 EGF20 の安定性を増強する2019

    • Author(s)
      小川光貴,坂口大和,竹内英之,岡島徹也
    • Organizer
      第83回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Notch 受容体上のO-結合型糖鎖修飾の質量分析計を用いた網羅的解析2019

    • Author(s)
      塚本庸平,妹尾勇弥,浦田悠輔,齊木颯,小川光貴,池田和貴,竹内英之,岡島徹也
    • Organizer
      第83回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] NOTCH受容体リガンドDelta-like 1 homologの細胞膜発現の制御機構についての解析2019

    • Author(s)
      田嶌優子,後藤和佳子,妹尾勇弥,塚本庸平,池田和貴,小川光貴,竹内英之,岡島徹也
    • Organizer
      第83回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2019 Research-status Report
  • [Book] 糖鎖生物学2020

    • Author(s)
      北島 健、佐藤 ちひろ、門松 健治、加藤 晃一
    • Total Pages
      306
    • Publisher
      名古屋大学出版会
    • ISBN
      9784815809812
    • Related Report
      2019 Research-status Report

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

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