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Clarification of novel glycan catabolic pathways by free glycan analysis of budding yeast and its application to human rare genetic disorders

Research Project

Project/Area Number 18H03990
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Tadashi Suzuki  国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (90345265)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2022: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2021: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2020: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2019: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2018: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Keywordsオリゴ糖転移酵素 / 遊離糖鎖 / ユビキチンリガーゼ / 初代肝細胞 / フォールディング / OST / STT3 / Doa10 / Hrd1 / 出芽酵母 / 先天性糖鎖不全症
Outline of Final Research Achievements

In S. cerevisiae, hydrolysis activity of OST was enhanced in hrd1 mutant, a ubiquitin ligase involved in endoplasmic reticulum-associated degradation (ERAD). After detailed analyses, it was found that formation of OST-mediated free glycans are enhanced under conditions of enhanced accumulation of unfolded proteins, such as ER stress conditions, and free glycans are suggested to play a role on promoting protein folding and/or preventing misfolded proteins from forming protein aggregates. On the other hand, in mammalian cells we established a method for analyzing serum free glycans, for which OST is believed to be involved in the formation, and identified several novel structures. Furthermore, using rat primary hepatocytes it was shown that liver is indeed involved in the secretion of OST-derived serum free glycans.

Academic Significance and Societal Importance of the Research Achievements

我々が新たに見出したオリゴ糖転移酵素の加水分解反応は、ドナー基質を加水分解する、という一見無駄な反応であるが、出芽酵母ではタンパク質のフォールディング促進やタンパク質凝集の抑制に関わる可能性が示された。一方哺乳動物細胞では、その加水分解反応が出芽酵母に比べて格段に促進されているが、肝臓が血清に遊離糖鎖を放出できるように進化的に獲得した機能であることが推察される。血清遊離糖鎖の機能はまだ不明であるが、さまざまな免疫反応の調整に関わる可能性が考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (37 results)

All 2022 2021 2020 2019 2018

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 17 results,  Open Access: 10 results) Presentation (17 results) (of which Int'l Joint Research: 10 results,  Invited: 8 results) Book (3 results)

  • [Journal Article] Mitotic phosphorylation inhibits the Golgi mannosidase MAN1A1.2022

    • Author(s)
      Huang S, Haga Y, Li J, Zhang J, Kweon HK, Seino J, Hirayama H, Fujita M, Moremen KW, Andrews P, Suzuki T, Wang Y.
    • Journal Title

      Cell Reports

      Volume: 41 Issue: 8 Pages: 111679-111679

    • DOI

      10.1016/j.celrep.2022.111679

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Luminescence detection of peptide:<i>N</i>-glycanase activity using engineered split inteins2022

    • Author(s)
      Takahashi Tsuyoshi、Uchibayashi Tatsuya、Ishii Nozomi、Matsuo Ichiro、Yoshida Yukiko、Suzuki Tadashi
    • Journal Title

      Chemical Communications

      Volume: 58 Issue: 95 Pages: 13282-13285

    • DOI

      10.1039/d2cc04865e

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ngly1-/- rats develop neurodegenerative phenotypes and pathological abnormalities in their peripheral and central nervous systems.2020

    • Author(s)
      M. Asahina, R. Fujinawa, S. Nakamura, K. Yokoyama, R. Tozawa, and T. Suzuki*
    • Journal Title

      Human Molecular Genetics

      Volume: 29 Issue: 10 Pages: 1635-1647

    • DOI

      10.1093/hmg/ddaa059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The ER-associated protease Ste24 prevents N-terminal signal peptide?independent translocation into the ER in Saccharomyces cerevisiae2020

    • Author(s)
      Hosomi Akira、Iida Kazuko、Cho Toshihiko、Iida Hidetoshi、Kaneko Masashi、Suzuki Tadashi
    • Journal Title

      Journal of Biological Chemistry

      Volume: in press Issue: 30 Pages: 10406-10419

    • DOI

      10.1074/jbc.ra120.012575

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytosolic N-GlcNAc proteins are formed by the action of endo-beta-N-acetylglucosaminidase.2020

    • Author(s)
      J. C. Maynard, H. Fujihira, G. E. Dolgonos, T. Suzuki* and A. L. Burlingame
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 539 Issue: 4 Pages: 719-724

    • DOI

      10.1016/j.bbrc.2020.06.127

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation.2020

    • Author(s)
      A. Galeone, J. M. Adams, S. Matsuda, M. F. Presa, A. Pandey, S. Y. Han, Y. Tachida, H. Hirayama, T. Vaccari, T. Suzuki, C. Lutz, M. Affolter, A. Zuberi, and H. Jafar-Nejad
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.55596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycometabolic Regulation of the Biogenesis of Small Extracellular Vesicles2020

    • Author(s)
      Harada Yoichiro、Nakajima Kazuki、Suzuki Takehiro、Fukushige Tomoko、Kondo Kiyotaka、Seino Junichi、Ohkawa Yuki、Suzuki Tadashi、Inoue Hiromasa、Kanekura Takuro、Dohmae Naoshi、Taniguchi Naoyuki、Maruyama Ikuro
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 2 Pages: 108261-108261

    • DOI

      10.1016/j.celrep.2020.108261

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The occurrence of nonglycosylated forms of N-glycoprotein upon proteasome inhibition does not confirm cytosolic deglycosylation.2020

    • Author(s)
      Huang C, Suzuki T.
    • Journal Title

      FEBS Lett.

      Volume: 594 Issue: 9 Pages: 1433-1442

    • DOI

      10.1002/1873-3468.13734

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional glycomics: Application to medical science and hepatology.2020

    • Author(s)
      Miyoshi E, Kamada Y, Suzuki T.
    • Journal Title

      Hepatol Res.

      Volume: 50 Issue: 2 Pages: 153-164

    • DOI

      10.1111/hepr.13459

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver-specific deletion of Ngly1 causes abnormal nuclear morphology and lipid metabolism under food stress2020

    • Author(s)
      Fujihira Haruhiko、Masahara-Negishi Yuki、Akimoto Yoshihiro、Hirayama Hiroto、Lee Hyeon-Cheol、Story Benjamin A.、Mueller William F.、Jakob Petra、Clauder-M?nster Sandra、Steinmetz Lars M.、Radhakrishnan Senthil K.、Kawakami Hayato、Kamada Yoshihiro、Miyoshi Eiji、Yokomizo Takehiko、Suzuki Tadashi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1866 Issue: 3 Pages: 165588-165588

    • DOI

      10.1016/j.bbadis.2019.165588

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NGLY1-Deficiency and the Non-Lysosomal Degradation of Free <i>N</i>-Glycans2019

    • Author(s)
      Suzuki T
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 31 Issue: 181 Pages: SE55-SE56

    • DOI

      10.4052/tigg.1926.2SE

    • NAID

      130007683657

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2019-07-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Free Glycans Derived From O-mannosylated Glycoproteins Suggest the Presence of an O-glycoprotein Degradation Pathway in Yeast2019

    • Author(s)
      Hirayama H, Matsuda T, Tsuchiya Y, Oka R, Seino J , Huang C, Nakajima K , Noda Y, Shichino Y, Iwasaki S , Suzuki T
    • Journal Title

      J Biol Chem

      Volume: 294(44) Issue: 44 Pages: 15900-15900

    • DOI

      10.1074/jbc.ra119.009491

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response2019

    • Author(s)
      Fermaintt Charles S.、Sano Kanae、Liu Zhida、Ishii Nozomi、Seino Junichi、Dobbs Nicole、Suzuki Tadashi、Fu Yang-Xin、Lehrman Mark A.、Matsuo Ichiro、Yan Nan
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 2377-2377

    • DOI

      10.1038/s41467-019-10319-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA tags used to image sugar-bearing proteins on cells.2018

    • Author(s)
      Suzuki T.
    • Journal Title

      Nature

      Volume: 561 Issue: 7721 Pages: 38-40

    • DOI

      10.1038/d41586-018-06092-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N-glycanase NGLY1 regulates mitochondrial homeostasis and inflammation through NRF1.2018

    • Author(s)
      Kun Yang, Ryan Huang, Haruhiko Fujihira, Tadashi Suzuki, Nan Yan
    • Journal Title

      Journal of Experimental Medicine

      Volume: 215(10) Issue: 10 Pages: 2600-2616

    • DOI

      10.1084/jem.20180783

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enrichment and characterization of a bacterial mixture capable of utilizing C-mannosyl tryptophan as a carbon source2018

    • Author(s)
      Hossain Tanim J.、Manabe Shino、Ito Yukishige、Iida Toshiya、Kosono Saori、Ueda Kenji、Hosomi Akira、Inoue Daishi、Suzuki Tadashi
    • Journal Title

      Glycoconjugate Journal

      Volume: 35 Issue: 2 Pages: 165-176

    • DOI

      10.1007/s10719-017-9807-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A New Fluorogenic Probe for the Detection of endo‐β‐N‐Acetylglucosaminidase2018

    • Author(s)
      Nozomi Ishii, Chie Sunaga, Kanae Sano, Chengcheng Huang, Kenta Iino, Yuji Matsuzaki, Tadashi Suzuki, Ichiro Matsuo
    • Journal Title

      ChemBioChem

      Volume: 19 Issue: 7 Pages: 660-663

    • DOI

      10.1002/cbic.201700662

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] NGLY1 欠損症研究の最前線2022

    • Author(s)
      鈴木 匡
    • Organizer
      T-CiRA オンラインセミナー (4月20日)
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Analysis of free N-glycans in fish serum.2022

    • Author(s)
      Akinobu Honda, Junichi Seino, and Tadashi Suzuki
    • Organizer
      SIALOGLYCO2022 (Nagoya) (9月6-8日)
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Can hepatocytes secrete free oligosaccharides? - possible mechanism for the occurrence of serum free oligosaccharides2022

    • Author(s)
      Chengcheng Huang, Junichi Seino, Haruhiko Fujihira, Di Wu, Shuichi Nakaya, Ken Kitajima, Chihiro Sato, and Tadashi Suzuki
    • Organizer
      SIALOGLYCO2022 (Nagoya) (9月7日)口頭発表:Chengcheng Huang
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血清中遊離 糖鎖の生成機構の研究2022

    • Author(s)
      黄澄澄、清野淳一、藤平陽彦、呉迪、中家修一、北島健、佐藤ちひろ、鈴木匡
    • Organizer
      第 41 回日本糖質学会年会(大阪) (9月29日)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Possible mechanism for the occurrence of serum free oligosaccharides.2022

    • Author(s)
      黄澄澄、清野淳一、呉迪、北島健、佐藤ちひろ、鈴木匡
    • Organizer
      第 95 回 日 本 生 化 学 会 大 会 ( 名 古 屋 )(11月10日)
    • Related Report
      2022 Annual Research Report
  • [Presentation] NGLY1 deficiency and non-lysosomal catabolism of glycans.2021

    • Author(s)
      Tadashi Suzuki
    • Organizer
      International conference on the biology of resilience and extreme longevity
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞質における糖鎖生物学-細胞恒常性維持の包括的理解を目指して2020

    • Author(s)
      鈴木 匡
    • Organizer
      第43回日本分子生物学会フォーラム AMED-CREST/PRIME 研究開発領域紹介:「プロテオスタシスの理解と革新的医療の創出
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 血清中シアリル遊離糖鎖の研究2019

    • Author(s)
      黄 澄澄、清野淳一、藤平陽彦、鈴木 匡
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ”誰もやってない研究”をやることは無謀なことか?2019

    • Author(s)
      鈴木 匡
    • Organizer
      第38回日本糖質学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Is NGLY1-deficiency a result of defective ER-associated degradation?2019

    • Author(s)
      Tadashi Suzuki
    • Organizer
      25th International Symposium on Glycoconjugates (Glyco25)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation and degradation of free oligosaccharides.2019

    • Author(s)
      Tadashi Suzuki
    • Organizer
      18th Human Proteome Organization (HUPO) World Congress/2nd Australasian Glycoscience Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Free oligosaccharides - formation and degradation2019

    • Author(s)
      Tadashi Suzuki
    • Organizer
      1st International Symposium on Glycans
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 血清にあるシアリル糖鎖の研究2018

    • Author(s)
      黄 澄澄、清野淳一、藤平陽彦、鈴木 匡
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Is NGLY1-deficiency a result of defective ER-associated degradation?2018

    • Author(s)
      Tadashi Suzuki
    • Organizer
      29th International Carbohydrate Symposium (ICS2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Toward curing NGLY1-deficiency2018

    • Author(s)
      Tadashi Suzuki
    • Organizer
      Benzon Symposium No. 64 GLYCOTHERAPEUTICS - emerging roles of glycans and medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] NGLY1-deficiency: Not just a defect in ERAD??2018

    • Author(s)
      Tadashi Suzuki
    • Organizer
      EMBO Workshop endoplasmic reticulum function in health and disease
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Studies on the serum sialyl oligosaccharides2018

    • Author(s)
      Chengcheng Huang, Junichi Seino, Haruhiko Fujihira and Tadashi Suzuki
    • Organizer
      Benzon Symposium No. 64 GLYCOTHERAPEUTICS - emerging roles of glycans and medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] Essentials of Glycobiology, 4th edition. Chapter 39 Glycans in Glycoprotein Quality Control2022

    • Author(s)
      Tadashi Suzuki, Richard D. Cummings, Markus Aebi, Armando Parodi
    • Total Pages
      9
    • Publisher
      Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press
    • ISBN
      1621824217
    • Related Report
      2022 Annual Research Report
  • [Book] Essentials of Glycobiology, 4th edition. Chapter 44, Genetic Disorders of Glycan Degradation2022

    • Author(s)
      Hudson H. Freeze, Richard Steet, Tadashi Suzuki, Taroh Kinoshita, Ronald L. Schnaar
    • Total Pages
      16
    • Publisher
      Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press
    • ISBN
      1621824217
    • Related Report
      2022 Annual Research Report
  • [Book] Reference Module in Chemistry, Molecular Sciences and Chemical Engineering2020

    • Author(s)
      Tadashi Suzuki and Haruhiko Fujihira
    • Total Pages
      28
    • Publisher
      Elsevier
    • ISBN
      9780124095472
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2025-01-30  

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