2022 Fiscal Year Final Research Report
Mechanisms of cancer and Alzheimer's disease involving glycan branching
Project/Area Number |
20H03207
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 43030:Functional biochemistry-related
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Research Institution | Gifu University |
Principal Investigator |
Kizuka Yasuhiko 岐阜大学, 糖鎖生命コア研究所, 教授 (20564743)
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Co-Investigator(Kenkyū-buntansha) |
中嶋 和紀 岐阜大学, 糖鎖生命コア研究所, 准教授 (10442998)
中の 三弥子 広島大学, 統合生命科学研究科(先), 准教授 (40397724)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 糖鎖 / 糖転移酵素 / bisecting GlcNAc / がん / アルツハイマー病 / GnT-III (MGAT3) / GnT-V (MGAT5) / GnT-IVa (MGAT4A) |
Outline of Final Research Achievements |
In this study, to understand the mechanisms by which glycan structures are changed upon disease development, we focus on glycosyltransferases in terms of their activity regulation and substrate specificity. As a result, regarding a cancer-related enzyme GnT-V, we found that its secretion is regulated, that it is loaded into small extracellular vesicles (sEVs) and transferred to recipient cells more glycan remodeling and that its non-catalytic domain is essential for activity toward glycoproteins. Moreover, regarding a diabetes-related enzyme GnT-IV, we found that it has a novel C-terminal lectin domain and that two GnT-IV isozymes a and b show different protein selectivity.
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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、疾患に関わるN型糖鎖合成酵素について、これまで不明であった基質タンパク質選択性や細胞内活性の新たな制御メカニズムを複数明らかにした。糖鎖は様々な疾患に深く関わることが知られているが、その発現メカニズムの複雑さから、糖鎖を標的とした創薬はまだ十分に行われていない。本研究は、これまで不可能であったタンパク質特異的な糖鎖修飾や、そのための新たな化合物開発へ有用な知見を与えるものであり、将来的な糖鎖標的創薬に大きく貢献するものである。
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