| Project/Area Number |
17K07353
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | プロテオグリカン / グリコサミノグリカン / コンドロイチン硫酸 / 硫酸化糖鎖 / ヘパラン硫酸 / 硫酸基転移酵素 / ゴルジ体ストレス応答 |
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| Outline of Final Research Achievements |
Proteoglycans (PGs) are cell-surface and extracellular matrix macromolecules that comprise a core protein to which glycosaminoglycan (GAG) chains are attached. The GAG moiety is essential for the PG functions. Thus, it is considered that cells are equipped with mechanisms that ensure proper GAG synthesis. Recently, Yoshida, H. et al. has reported that the TFE3 pathway allows the Golgi apparatus to regulate protein glycosylation to accommodate cellular demands. In this study, we have examined whether GAG biosynthesis is regulated by the TFE3 pathway. Overexpression of PG core proteins activated TFE3 and induced the expression of GAG biosynthetic enzymes, to sustain proper PG synthesis. In addition, we investigated the biological significance of the TFE3 pathway during neuronal differentiation. Knockdown of TFE3 inhibited neuronal differentiation. Furthermore, we found the small compound which activates TFE3.
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| Academic Significance and Societal Importance of the Research Achievements |
コアタンパク質にグリコサミノグリカン (GAG) と呼ばれる直鎖状の硫酸化糖鎖が付加したプロテオグリカン (PG) は, 細胞表面や細胞外マトリクスに存在し, 細胞の増殖・分化をはじめとする種々の機能を制御する. 本研究で, コアタンパク質の合成増大に応じて GAG 鎖の合成が制御される仕組みを見出したこと, このような制御経路が神経分化過程で働いることを示したことに学術的意義がある. さらに, この制御経路に関わる転写因子の活性化を引き起こす低分子化合物を見出し, これが神経分化を促進することを明らかにした点に社会的意義がある.
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