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Revealing the physiological function of de-N-glycosylating enzymes in mice

Research Project

Project/Area Number 16K18520
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionJuntendo University

Principal Investigator

Fujihira Haruhiko  順天堂大学, 医学部, 特任研究員 (50721057)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsNgly1 / ENGase / ubiquitin-proteasome / autophagy / 糖鎖脱離酵素 / PNGase / ERAD / Autophagy / ユビキチン・プロテアソーム / オートファジー
Outline of Final Research Achievements

In this study, I aimed to reveal an unknown physiological function of de-N-glycosylating enzymes, peptide:N-glycanase (Ngly1) and endo-beta-N-acetylglucosaminidase (ENGase), in mammals. To this end, I performed phenotypic analyses of mice that lack Ngly1/Engase gene (Ngly1-KO, Engase-KO, Ngly1;Engase-KO mice). I found that the deletion of Ngly1 causes many defects (heart, muscle, nervous systems, body weight etc), while Engase deletion does not cause any defects. Interestingly, the defects caused by the loss of Ngly1 are partially rescued by the additional deletion of Engase gene. Therefore, there are two types of pathways that cause the defects by Ngly1-deletion, ENGase-dependent pathway and ENGase-independent pathway. Based on recent reports and my additional experiments suggested that a transcriptional factor Nrf1, which regulates the expression levels of proteasome subunits under low proteasome activity, seems to be involved in the ENGase-independent pathway.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity2018

    • Author(s)
      Fujihira H, Usami K, Matsuno K, Takeuchi H, Denda-Nagai K, Furukawa JI, Shinohara Y, Takada A, Kawaoka Y, Irimura T
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 5495-5495

    • DOI

      10.1038/s41598-018-23357-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 60年間の研究から得た教訓2017

    • Author(s)
      藤平陽彦、鈴木匡
    • Journal Title

      生化学

      Volume: 89 Issue: 5 Pages: 599-599

    • DOI

      10.14952/SEIKAGAKU.2017.890599

    • ISSN
      0037-1017
    • Year and Date
      2017-10-25
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lethality of mice bearing a knockout of the Ngly1-gene is rescued by the additional deletion of the Engase gene.2017

    • Author(s)
      Fujihira H., Masahara-Negishi Y., Tamura M., Harada Y., Chengcheng H., Wakana S., Taniguchi N., Kondoh G., Yamashita T., Funakoshi Y. and Suzuki T.
    • Journal Title

      PLOS Genetics

      Volume: 13 Issue: 4 Pages: 1-23

    • DOI

      10.1371/journal.pgen.1006696

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The defects caused by the loss of Ngly1 can be partially rescued by the additional deletion of Engase2018

    • Author(s)
      Haruhiko Fujihira, Yuki Masahara-Negishi, Masaru Tamura, Shigeharu Wakana, Daisuke Takakura, Nana Kawasaki, Yoko Funakoshi, Tadashi Suzuki
    • Organizer
      International Symposium on ER Stress, glycosylation, homeostasis and diseases
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Engase欠損により回避可能/不可能なNgly1-KOマウスの表現型2017

    • Author(s)
      藤平陽彦
    • Organizer
      第3回 ENGase研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Summary of phenotypic analyses of Ngly1-KO mice and Ngly1/Engase-KO mice2017

    • Author(s)
      Haruhiko Fujihira, Yuki Masahara-Negishi, Masaru Tamura, Shigeharu Wakana, Daisuke Takakura, Nana Kawasaki, Yoko Funakoshi, Tadashi Suzuki
    • Organizer
      International Syposium “Systems Glycobiology and Beyond”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Engase欠損により回避可能/不可能なNgly1欠損による異常2017

    • Author(s)
      藤平陽彦、根岸-正原由紀、田村勝、高倉大輔、黄澄澄、若菜茂晴、川崎ナナ、船越陽子、鈴木匡
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Physiological function of deglycosylating enzymes acting on N-glycans in mice2016

    • Author(s)
      Haruhiko Fujihira, Yuki Masahara-Negishi, Masaru Tamura, Shigeharu Wakana, Daisuke Takakura, Nana Kawasaki, Yoko Funakoshi, Tadashi Suzuki
    • Organizer
      Frontiers 2016 symposium
    • Place of Presentation
      EPFL (Ecole Polytechnique Federale de Lausanne) (Switzerland)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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