Integrated analysis of atypical glycosylation as a basis for precise regulation of Notch signaling in the vascular endothelium

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03416
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Nagoya University
• Principal Investigator: Okajima Tetsuya 名古屋大学, 医学系研究科, 教授 (20420383)
• Co-Investigator(Kenkyū-buntansha): 小川 光貴 名古屋大学, 医学系研究科, 助教 (70727429) ; 竹内 英之 静岡県立大学, 薬学部, 教授 (80361608)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: O-GlcNAc / EOGT / NOTCH / vascular permeability

Outline of Final Research Achievements

To understand the molecular mechanism of precise regulation of NOTCH signaling via the O-GlcNAc transferase EOGT, this project clarified the basic mode of O-GlcNAc glycan structure that modifies NOTCH1 and developed a new analytical tool to clarify the dynamics of O-GlcNAc modification in vivo. We also succeeded in demonstrating the cooperative action of EOGT and other glycosyltransferases in the regulation of NOTCH signaling and the localization of EOGT expression in specific vascular endothelium and its involvement with vascular permeability.

Free Research Field

生化学、糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発されたO-GlcNAc修飾の動態解析ツールを用いることで、生理的な刺激や病的な状況でのO-GlcNAc修飾の時空間的な制御機構の解明に貢献することが期待される。また、EOGTが血管内皮に特異的な発現を示すことや、細胞の癌化に伴い異所性にEOGT発現が誘導されることから、EOGTを分子標的にした新しい治療戦略が考えられる。