Elucidation of the mechanism of activity control by polymerization of ACC
| Project/Area Number |
20K21292
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 38:Agricultural chemistry and related fields
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| Research Institution | Tokyo University of Agriculture |
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Principal Investigator |
Inoue Jun 東京農業大学, 応用生物科学部, 教授 (70323962)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 脂肪酸合成 / アセチルCoAカルボキシラーゼ / ポリマー化 / ACC / ポリマー / 脂質代謝 |
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| Outline of Research at the Start |
本研究の目的は、アセチルCoAカルボキシラーゼ（ACC）活性制御機構を明らかにし、余剰エネルギーを脂肪として蓄積する分子機構の解明を目指すと共に、ACC二量体やポリマーの構成因子の同定・解析を行うことで、小分子化合物（食品成分や医薬品）によるACC活性制御実現に向けた新たな方向性を提示することである。これまでのACC阻害剤はACC二量体やポリマー形成に作用する例は知られておらず、本研究により肥満抑制や糖尿病改善の新規な作用点の解明を目指す。
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| Outline of Final Research Achievements |
In this study, we investigated the regulatory mechanism of ACC activity, which is the rate-limiting enzyme for fatty acid synthesis. ACC activity is known to be promoted by its polymerization. We identified the binding regions between ACC and MIG12, which is ACC polymerization-promoting factor. We also showed that mutation of the leucine zipper domain on the C-terminal region of MIG12 greatly attenuates its binding. Furthermore, we succeeded in constructing an evaluation system to analyze ACC activity in vitro.
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| Academic Significance and Societal Importance of the Research Achievements |
ACCの活性抑制は抗肥満や抗糖尿病につながり、今回の研究成果は新たな阻害剤開発のツールとして利用できる。酵素のポリマー化による活性化の例は少なく、MIG12によるACCポリマー化制御機構の解明は学術的に貴重な事例になる。
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Report
(4 results)
Research Products
(3 results)
