| Project/Area Number |
20K06546
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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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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ユビキチン / HIF / 糖代謝 / ユビキチン様タンパク質 / マクロファージ / 分子シャペロン / 細胞増殖 / 糖代謝制御 / 細胞増殖調節 |
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| Outline of Research at the Start |
申請者は、ユビキチン様タンパク質である Monoclonal Nonspecific Suppressor Factor β （MNSFβ）を発見し、アポトーシスや細胞分化の調節機能について明らかにしてきた。
本研究の目的は、ユビキチン様タンパク質MNSFβの解糖系促進作用による、細胞増殖調節の機序解明である。本機序に関わる解糖系酵素の一部を既に同定し、HIF-1αの関与も認めている。MNSFβによる糖代謝調節とHIF-1α発現の制御を介した細胞増殖調節機構を解明し、抗がん創薬につなげる。
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| Outline of Final Research Achievements |
Monoclonal non-specific suppressor factor β (MNSFβ) is a ubiquitously expressed member of the ubiquitin-like family that has been involved in various biological functions. Previous studies have demonstrated that MNSFβ regulates glycolysis and enhances cell proliferation in the macrophage-like cell line RAW264.7. In this study, we showed that MNSFβ regulates HIF-1α-mediated metabolic reprogramming. In RAW264.7 cells, MNSFβ siRNA increased oxygen consumption rate and ROS production, but decreased ATP levels. The rate of ATP reduction upon addition of oligomycin, an inhibitor of mitochondrial ATP synthase, was significantly greater in cells with MNSFβ knockdown. In addition, the expression levels of HIF-1α protein and mRNA were decreased by MNSFβ siRNA. The effect of MNSFβ on glucose metabolism was examined in murine peritoneal macrophages, but there were no changes in lactate production, glucose consumption, or ROS production.
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| Academic Significance and Societal Importance of the Research Achievements |
ユビキチン様タンパク質MNSFβの役割として、世界で初めて糖代謝制御機能について詳細に明らかにした。この研究成果は、本研究領域へ与えるインパクトは極めて大きい。これまでアポトーシス制御など多様な機能について明確にしてきたが、今回の研究成果により、MNSFβは生命の根幹に関与する機能を有すると推察される。
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