• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanisms of cancer and Alzheimer's disease involving glycan branching

Research Project

Project/Area Number 20H03207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionGifu University

Principal Investigator

Kizuka Yasuhiko  岐阜大学, 糖鎖生命コア研究所, 教授 (20564743)

Co-Investigator(Kenkyū-buntansha) 中嶋 和紀  岐阜大学, 糖鎖生命コア研究所, 准教授 (10442998)
中の 三弥子  広島大学, 統合生命科学研究科(先), 准教授 (40397724)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords糖鎖 / 糖転移酵素 / bisecting GlcNAc / がん / アルツハイマー病 / GnT-III (MGAT3) / GnT-V (MGAT5) / GnT-IVa (MGAT4A)
Outline of Research at the Start

本研究では、がん・アルツハイマー病(AD)に関わる糖鎖分岐構造に着目し、疾患時に起きる糖鎖の発現変化がどのようにこれらの疾患を悪性化していくのか、そのメカニズムを明らかにする。特に、ADではbisecting GlcNAc分岐、がんではbeta1,6分岐の2つの糖鎖分岐構造に着目し、これらの糖鎖が特定の標的タンパク質に発現するメカニズムや、タンパク質の機能変化の詳細について明らかにすることで、がん・ADにおける糖鎖の分岐形成メカニズムとその意義を解明する。

Outline of Final Research Achievements

In this study, to understand the mechanisms by which glycan structures are changed upon disease development, we focus on glycosyltransferases in terms of their activity regulation and substrate specificity. As a result, regarding a cancer-related enzyme GnT-V, we found that its secretion is regulated, that it is loaded into small extracellular vesicles (sEVs) and transferred to recipient cells more glycan remodeling and that its non-catalytic domain is essential for activity toward glycoproteins. Moreover, regarding a diabetes-related enzyme GnT-IV, we found that it has a novel C-terminal lectin domain and that two GnT-IV isozymes a and b show different protein selectivity.

Academic Significance and Societal Importance of the Research Achievements

本研究では、疾患に関わるN型糖鎖合成酵素について、これまで不明であった基質タンパク質選択性や細胞内活性の新たな制御メカニズムを複数明らかにした。糖鎖は様々な疾患に深く関わることが知られているが、その発現メカニズムの複雑さから、糖鎖を標的とした創薬はまだ十分に行われていない。本研究は、これまで不可能であったタンパク質特異的な糖鎖修飾や、そのための新たな化合物開発へ有用な知見を与えるものであり、将来的な糖鎖標的創薬に大きく貢献するものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (6 results) Journal Article (16 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 11 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Remarks (6 results)

  • [Int'l Joint Research] University of Mississippi(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Jiangnan University(中国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Mississippi(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Jiangnan University(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Georgia(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] National University of Ireland(アイルランド)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells2023

    • Author(s)
      Hirata Tetsuya、Harada Yoichiro、Hirosawa Koichiro M.、Tokoro Yuko、Suzuki Kenichi G.N.、Kizuka Yasuhiko
    • Journal Title

      iScience

      Volume: 26 Issue: 1 Pages: 105747-105747

    • DOI

      10.1016/j.isci.2022.105747

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The stem region of α1,6-fucosyltransferase FUT8 is required for multimer formation but not catalytic activity2022

    • Author(s)
      Tomida Seita、Nagae Masamichi、Kizuka Yasuhiko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 12 Pages: 102676-102676

    • DOI

      10.1016/j.jbc.2022.102676

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ER entry pathway and glycosylation of GPI-anchored proteins are determined by N-terminal signal sequence and C-terminal GPI-attachment sequence2022

    • Author(s)
      Hirata Tetsuya、Yang Jing、Tomida Seita、Tokoro Yuko、Kinoshita Taroh、Fujita Morihisa、Kizuka Yasuhiko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 10 Pages: 102444-102444

    • DOI

      10.1016/j.jbc.2022.102444

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Examination of differential glycoprotein preferences of N-acetylglucosaminyltransferase-IV isozymes a and b2022

    • Author(s)
      Osada Naoko、Nagae Masamichi、Nakano Miyako、Hirata Tetsuya、Kizuka Yasuhiko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 9 Pages: 102400-102400

    • DOI

      10.1016/j.jbc.2022.102400

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shedding of N-acetylglucosaminyltransferase-V is regulated by maturity of cellular N-glycan2022

    • Author(s)
      Hirata Tetsuya、Takata Misaki、Tokoro Yuko、Nakano Miyako、Kizuka Yasuhiko
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 743-743

    • DOI

      10.1038/s42003-022-03697-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A)2022

    • Author(s)
      Nagae Masamichi、Hirata Tetsuya、Tateno Hiroaki、Mishra Sushil K.、Manabe Noriyoshi、Osada Naoko、Tokoro Yuko、Yamaguchi Yoshiki、Doerksen Robert J.、Shimizu Toshiyuki、Kizuka Yasuhiko
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 695-695

    • DOI

      10.1038/s42003-022-03661-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic utilization and remodeling of glycan biosynthesis using fucose analogs2022

    • Author(s)
      Kizuka Yasuhiko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1866 Issue: 12 Pages: 130243-130243

    • DOI

      10.1016/j.bbagen.2022.130243

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-based design of UDP-GlcNAc analogs as candidate GnT-V inhibitors2022

    • Author(s)
      Vibhute Amol M.、Tanaka Hide-nori、Mishra Sushil K.、Osuka Reina F.、Nagae Masamichi、Yonekawa Chizuko、Korekane Hiroaki、Doerksen Robert J.、Ando Hiromune、Kizuka Yasuhiko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1866 Issue: 6 Pages: 130118-130118

    • DOI

      10.1016/j.bbagen.2022.130118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] N-acetylglucosaminyltransferase-V requires a specific noncatalytic luminal domain for its activity toward glycoprotein substrates.2022

    • Author(s)
      Osuka RF, Hirata T, Nagae M, Nakano M, Shibata H, Okamoto R, Kizuka Y.
    • Journal Title

      J. Biol. Chem.

      Volume: 298 Issue: 3 Pages: 101666-101666

    • DOI

      10.1016/j.jbc.2022.101666

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue-Specific Regulation of HNK-1 Biosynthesis by Bisecting GlcNAc2021

    • Author(s)
      Kawade Haruka、Morise Jyoji、Mishra Sushil K.、Tsujioka Shuta、Oka Shogo、Kizuka Yasuhiko
    • Journal Title

      Molecules

      Volume: 26 Issue: 17 Pages: 5176-5176

    • DOI

      10.3390/molecules26175176

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptide Sequence Mapping around Bisecting GlcNAc-Bearing N-Glycans in Mouse Brain.2021

    • Author(s)
      Ohkawa Y, Kizuka Y, Takata M, Nakano M, Ito E, Mishra SK, Akatsuka H, Harada Y, Taniguchi N.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Issue: 16 Pages: 8579-8579

    • DOI

      10.3390/ijms22168579

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] N-Glycosylation2021

    • Author(s)
      Hirata Tetsuya、Kizuka Yasuhiko
    • Journal Title

      Adv. Exp. Med. Biol.

      Volume: 1325 Pages: 3-24

    • DOI

      10.1007/978-3-030-70115-4_1

    • ISBN
      9783030701147, 9783030701154
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of protein arginine methyltransferase 1 (PRMT1) in brain development and disease2021

    • Author(s)
      Hashimoto Misuzu、Fukamizu Akiyoshi、Nakagawa Tsutomu、Kizuka Yasuhiko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1865 Issue: 1 Pages: 129776-129776

    • DOI

      10.1016/j.bbagen.2020.129776

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V2020

    • Author(s)
      Hirata Tetsuya、Nagae Masamichi、Osuka Reina F.、Mishra Sushil K.、Yamada Mayumi、Kizuka Yasuhiko
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1864 Issue: 12 Pages: 129726-129726

    • DOI

      10.1016/j.bbagen.2020.129726

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs2020

    • Author(s)
      Ma Chenyu、Takeuchi Hideyuki、Hao Huilin、Yonekawa Chizuko、Nakajima Kazuki、Nagae Masamichi、Okajima Tetsuya、Haltiwanger Robert S.、Kizuka Yasuhiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 17 Pages: 6007-6007

    • DOI

      10.3390/ijms21176007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The SH3 domain in the fucosyltransferase FUT8 controls FUT8 activity and localization and is essential for core fucosylation2020

    • Author(s)
      Tomida Seita、Takata Misaki、Hirata Tetsuya、Nagae Masamichi、Nakano Miyako、Kizuka Yasuhiko
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 23 Pages: 7992-8004

    • DOI

      10.1074/jbc.ra120.013079

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ゴルジ体におけるN型糖鎖の成熟過程を制御する小胞体2022

    • Author(s)
      木塚康彦
    • Organizer
      第45回日本分子学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 糖転移酵素のタンパク質選択性を標的としたGlycoscience2022

    • Author(s)
      木塚康彦
    • Organizer
      第41回日本糖質学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Protein selective actions of N-glycan branching enzymes2022

    • Author(s)
      Kizuka Y.
    • Organizer
      UGLIP Seminar
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] N型糖鎖の枝分かれの生化学2021

    • Author(s)
      木塚康彦
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] がん関連糖転移酵素GnT-Vの発現制御と標的選択のメカニズム2021

    • Author(s)
      木塚康彦
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Insights into protein-selective action of GnT-V2021

    • Author(s)
      4. Kizuka Y.
    • Organizer
      The 3rd Australasian Glycoscience Symposium
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] SH3 domain of FUT8 is required for its enzymatic activity, cell surface localization and association with ribophorin l2020

    • Author(s)
      Kizuka Y.
    • Organizer
      Annual Meeting of the Society for Glycobiology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 糖尿病に関連する糖鎖合成酵素 GnT-IVaの新たな仕組みを発見

    • URL

      https://igcore.thers.ac.jp/wp_control/wp-content/uploads/79e08b70c6b99f0115ad4429a1b80905-2.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] がん関連糖鎖の生産を細胞内で制御する仕組みを解明

    • URL

      https://igcore.thers.ac.jp/wp_control/wp-content/uploads/3d811bd17be696246bda9b7ed4496859.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] 似て非なる酵素が糖鎖を作り分ける仕組みを解明

    • URL

      https://igcore.thers.ac.jp/wp_control/wp-content/uploads/9d99217b0a7305a88269c801ee6ef8a9.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] 酵素受け渡しによるがん関連糖鎖の新たな改変機構を解明

    • URL

      https://igcore.thers.ac.jp/wp_control/wp-content/uploads/d0e3b5afcaa2b7bc7f1c32fc567327e0.pdf

    • Related Report
      2022 Annual Research Report
  • [Remarks] がんの悪性化に関わる糖鎖合成酵素GnT-V は糖鎖をつけるタンパク質を選ぶ

    • URL

      https://www.gifu-u.ac.jp/about/publication/press/20220131.pdf

    • Related Report
      2021 Annual Research Report
  • [Remarks] 糖鎖合成酵素FUT8が働く新しい仕組みを発見

    • URL

      https://www.gifu-u.ac.jp/news/research/2020/05/entry07-7950.html

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi