2022 Fiscal Year Final Research Report
Significance of structural diversity of O-glucose glycans in Notch signaling
Project/Area Number |
19KK0195
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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Research Institution | University of Shizuoka (2021-2022) Nagoya University (2019-2020) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
田嶌 優子 名古屋大学, 医学系研究科, 講師 (10423104)
LO PEIWEN 名古屋大学, 医学系研究科, 外国人特別研究員 (20822406)
浦田 悠輔 名古屋大学, 医学部附属病院, 医員 (90897357)
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Project Period (FY) |
2019-10-07 – 2023-03-31
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Keywords | 糖鎖 / O-グルコース糖鎖修飾 / 糖転移酵素 / Notchシグナル |
Outline of Final Research Achievements |
Together with researchers from Japan, China, and the United States, the Principal Investigator has led the research field in reporting that O-glucose glycosylation of the Notch receptor is essential for its functional performance (Cell 2008, Nature Chemical Biology 2015, 2016, EMBO Mol Med 2016). In this international collaborative study, by taking advantage of the expertise of biochemistry, genetics, analytical chemistry, and structural biology, we discovered the previously unreported elongated structure of the O-glucose glycosylation at specific EGF repeats in the Notch receptors, and revealed its functional importance in the fine-tuning of Notch signaling and the glycosyltransferases involved in its biosynthesis for the first time in the world.
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Free Research Field |
糖鎖生物学
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、多細胞生物において、さまざまな細胞の運命決定を担うNotch細胞間シグナル伝達の新しい糖鎖修飾による制御メカニズムを明らかにした。また、化学的および生物化学的手法を用いた多面的な解析により、新奇糖鎖修飾の構造と生合成を担う糖転移酵素を同定した。本研究の成果は、哺乳類の発生メカニズムに関する理解を深めるだけでなく、癌や、最近、注目を集めている統合失調症や非アルコール性肝疾患など、Notchシグナルの異常に起因する病態の診断、治療、予防法の開発に大きく貢献する可能性がある。
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