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Exploration and identification of novel C-mannosyltransferase

Research Project

Project/Area Number 17K15094
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionNational Institute of Advanced Industrial Science and Technology (2018)
Keio University (2017)

Principal Investigator

Niwa Yuki  国立研究開発法人産業技術総合研究所, 生命工学領域, 産総研特別研究員 (20756077)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsC型糖修飾 / 糖転移酵素 / DPY19 / C型糖転移酵素 / C-mannosylation / CRISPR/Cas9 / 糖鎖生物学
Outline of Final Research Achievements

The aim of this study is to explore and identify novel C-mannosyltransferase. In order to search for a novel C-mannosyltransferase, we designed first and second screening systems and validated these screening systems. However, another study suggested that the novel C-mannosyltransferase, which is the purpose of this study, may not exist. Thus, the verification is required. As a result, in S2 cells, which should not have C-mannosyltransferase activity, C-mannosylation was detected in a specific protein. Furthermore, as a result of knockout of dpy19 in S2 cells, reduction of C-mannosylation of this protein was confirmed. These results suggested that the novel C-mannosyltransferase may not exist.

Academic Significance and Societal Importance of the Research Achievements

本研究により、当初の目的としていた新規C型糖転移酵素は存在しない可能性が示唆された。これによりC型糖修飾の修飾機構はDPY19の経路のみである可能性が示唆され、C型糖修飾の機構と生物学的意義を考察していく上で学術的に意義深い結果が得られた。一方でショウジョウバエS2細胞の有するdpy19についても酵素活性を有する可能性が示唆され、これまで様々なタンパク質に対しC型糖転移酵素を示さなかった原因について探索することで新たな発見につながると考えられ、その結果からヒトにフィードバックすることで疾患との関連など、新たな発見につながる可能性を秘めており、その点においても意義深いと考えられる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (21 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] C-mannosylation of R-spondin2 activates Wnt/β-catenin signaling and migration activity in human tumor cells.2019

    • Author(s)
      Mizuta, H., Kuga, K., Suzuki, T., Niwa, Y., Dohmae, N. & Simizu, S.
    • Journal Title

      International Journal of Oncology

      Volume: - Pages: 2127-2138

    • DOI

      10.3892/ijo.2019.4767

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>C</i>-Mannosylation: Previous Studies and Future Research Perspectives2018

    • Author(s)
      Niwa Yuki、Simizu Siro
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 30 Issue: 177 Pages: E231-E238

    • DOI

      10.4052/tigg.1755.1E

    • NAID

      130007521332

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2018-11-25
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells.2018

    • Author(s)
      Kawahara, R., Niwa, Y. & Simizu, S.
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 8 Pages: 2490-2496

    • DOI

      10.1111/cas.13693

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Topological analysis of DPY19L3, a human C-mannosyltransferase2018

    • Author(s)
      Niwa Yuki、Nakano Yoshihiko、Suzuki Takehiro、Yamagishi Mizuo、Otani Kei、Dohmae Naoshi、Simizu Siro
    • Journal Title

      The FEBS Journal

      Volume: 285 Issue: 6 Pages: 1162-1174

    • DOI

      10.1111/febs.14398

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of granulocyte colony-stimulating factor receptor-mediated granulocytic differentiation by C -mannosylation2018

    • Author(s)
      Otani Kei、Niwa Yuki、Suzuki Takehiro、Sato Natsumi、Sasazawa Yukiko、Dohmae Naoshi、Simizu Siro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 498 Issue: 3 Pages: 466-472

    • DOI

      10.1016/j.bbrc.2018.02.210

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dpy-19 like 3-mediated C-mannosylation and expression levels of RPE-spondin in human tumor cell lines2017

    • Author(s)
      Morishita Shohei、Suzuki Takehiro、Niwa Yuki、Dohmae Naoshi、Simizu Siro
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 2 Pages: 2537-2544

    • DOI

      10.3892/ol.2017.6465

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] C-mannosylationによるR-spondin2の機能制御2018

    • Author(s)
      水田隼斗、丹羽祐貴、堂前直、清水史郎
    • Organizer
      第22回日本がん分子標的治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cytosporolide類の細胞増殖抑制活性における責任分子標的の同定2018

    • Author(s)
      大竹慶祐、室井誠、丹羽祐貴、宮嵜奏、笹澤有紀子、長田裕之、清水史郎
    • Organizer
      第22回日本がん分子標的治療学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of molecular targets on inhibitory activity of cell proliferation by cytosporolide analogs2018

    • Author(s)
      Otake, K., Muroi, M., Niwa, Y., Takao, K., Osada, H. & Simizu, S.
    • Organizer
      The 9th Japan-Korea Chemical Biology Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glucosyl-galactosyl-hydroxylation of CCN1 regulates its secretion2018

    • Author(s)
      Ishizawa, Y., Niwa, Y., Suzuki, T., Dohmae, N. & Simizu, S.
    • Organizer
      29th International Carbohydrate Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インテグリンβ1は血管擬態形成に重要な因子である2018

    • Author(s)
      川原遼太、丹羽祐貴、清水史郎
    • Organizer
      第27回日本がん転移学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] レクチンによるエクソソーム送達システムの開発2018

    • Author(s)
      丹羽祐貴、舘野浩章
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞由来エクソソームのグライコーム解析2018

    • Author(s)
      齊藤佐代子、箕嶋文、清井佳代、丹羽祐貴、舘野浩章
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] トポロジー解析によるDPY19L1の活性中心の探索2018

    • Author(s)
      横山典弘、柳原凌太郎、小松良亮、三浦一輝、丹羽祐貴、清水史郎
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CCN1におけるglucosyl-galactosyl- hydroxylationの機能解析2018

    • Author(s)
      石沢雄大、丹羽祐貴、鈴木健裕、堂前直、清水史郎
    • Organizer
      第37回日本糖質学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] R-spondin2のC型糖修飾はがんのバイオマーカーに成り得る2018

    • Author(s)
      水田隼斗、丹羽祐貴、清水史郎
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] トポロジー解析によるDPY19L1のC-mannosyltransferase活性中心の探索2018

    • Author(s)
      横山典弘、柳原凌太郎、三浦一輝、丹羽祐貴、清水史郎
    • Organizer
      日本農芸化学会関東支部2018年度支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] R-spondin1におけるリン酸化の機能解析2018

    • Author(s)
      西谷拓海、鈴木健裕、丹羽祐貴、三浦一輝、堂前直、清水史郎
    • Organizer
      日本農芸化学会関東支部2018年度支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Glucosyl-galactosyl-hydroxylation of CCN1regulates its secretion2018

    • Author(s)
      Yudai Ishizawa, Yuki Niwa, Takehiro Suzuki, Naoshi Dohmae, Siro Simizu
    • Organizer
      International Symposium on ER stress, glycosylation, homeostasis, and diseases
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型糖修飾酵素DPY19L3のトポロジー解析と活性点の探索2017

    • Author(s)
      丹羽祐貴、中野圭彦、鈴木健裕、山岸瑞生、大谷慧、堂前直、清水史郎
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] メラノソーム関連タンパク質PMELにおけるC-mannosylationの解析2017

    • Author(s)
      小松良亮、丹羽祐貴、鈴木健裕、清水映輪奈、堂前直、清水史郎
    • Organizer
      第36回日本糖質学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん細胞の血管擬態形成におけるintegrin beta1の役割解析2017

    • Author(s)
      川原遼太、丹羽祐貴、清水史郎
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Identification of membrane topology of human DPY19L3 reveals that C-terminal region is essential for C-mannosyltransferase activity2017

    • Author(s)
      Yuki Niwa, Yoshihiko Nakano, Takehiro Suzuki, Mizuo Yamagishi, Kei Otani, Naoshi Dohmae, Siro Simizu
    • Organizer
      24th International Symposium on Glycoconjugates
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Premelanosome Protein (PMEL) is C-Mannosylated at W104, W153 and W1562017

    • Author(s)
      Ryosuke Komatsu, Takehiro Suzuki, Yuki Niwa, Erina Shimizu, Naoshi Dohmae, Siro Simizu
    • Organizer
      24th International Symposium on Glycoconjugates
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 顆粒球コロニー刺激因子受容体のC型糖修飾はその機能に重要である2017

    • Author(s)
      丹羽祐貴、清水史郎
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトがん細胞における血管擬態はintegrin beta1依存的である2017

    • Author(s)
      川原遼太、丹羽祐貴、清水史郎
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Integrin β1 plays a crucial role on vasculogenic mimicry formation2017

    • Author(s)
      Ryota Kawahara, Yuki Niwa, Siro Simizu
    • Organizer
      AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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