| Project/Area Number |
17K05942
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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 |
Bio-related chemistry
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| Research Institution | Tokyo University of Science, Yamaguchi (2020)
Himeji Dokkyo University (2017-2019) |
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Principal Investigator |
Miyamoto Kazuhide 山陽小野田市立山口東京理科大学, 薬学部, 教授 (10415317)
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| Co-Investigator(Kenkyū-buntansha) |
砂川 真弓 (湯浅真弓) 姫路獨協大学, 薬学部, 助手 (40444509)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ユビキチン化 / バイオマーカ / がん診断 / ユビキチン |
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| Outline of Final Research Achievements |
Ubiquitin-conjugating (E2) enzymes of the ubiquitination pathway are associated with various cancers, such as leukemia, lung cancer, and gastric cancer. However, to date, detection of E2 activities is not practicable for capturing the pathological conditions of cancers due to complications related to the enzymatic cascade reaction. To overcome this hurdle, I have recently investigated a novel strategy for measuring E2 activities. Artificial RING fingers (ARFs) were developed to conveniently detect E2 activities during the ubiquitination reaction. ARFs were created by grafting the active sites of ubiquitin-ligating (E3) enzymes onto amino acid sequences with 38 residues. The use of the immunochromatography of the ARF and allowed us to monitor E2 activities using acute promyelocytic leukemia (APL)-derived cells following treatment with the anticancer drug bortezomib.
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| Academic Significance and Societal Importance of the Research Achievements |
生体内のユビキチン化反応のE2（ユビキチン結合酵素）活性を簡便に捉えることができる新しい検出システムの開発を進めている。血液・組織中のE2活性を測定すれば新たながん診断の指標となりうることは広く認識されながらも、ユビキチン化が複雑なカスケード反応であるという理由から、これまでE2活性を定量的に計測するのは困難とされてきた。世界で初めて、人工的にユビキチンリガーゼを分子設計し、これを活用した簡便なE2活性の定量的な検出システムの開発に成功した。今後の更なる研究の発展により、ユビキチン化活性に基づいた新たながん診断、例えば、医薬品の効果を治療前に予測できるがん診断が可能になると期待されている。
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