Identification of molecular mechanism underlying malignant mesothelioma development using conditional mouse model and search of therapeutic target molecules
| Project/Area Number |
18K08161
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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 53030:Respiratory medicine-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
南 俊行 兵庫医科大学, 医学部, 講師 (00705113)
吉川 良恵 兵庫医科大学, 医学部, 講師 (10566673)
大村谷 昌樹 兵庫医科大学, 医学部, 教授 (60398229)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 悪性中皮腫 / モデルマウス / トランスジェニックマウス / BAP1 / signal pathway / 遺伝子改変マウス |
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| Outline of Final Research Achievements |
BAP1 is a predisposition gene of malignant mesothelioma (MM), uveal melanoma, and so on. The antagonistic relationship between UBE2O, ubiquitin-conjugating enzyme, and BAP1, ubiquitin C-terminal hydrolase, was reported in 293T and U2OS cell lines; multi-monoubiquitination of the nuclear localization signal in BAP1 by UBE2O change to localization of BAP1 from nucleus to cytoplasm, and it would lead for BAP1 to lose DNA repair function. This interaction of UBE2O-BAP1 was not identified in the MM cell line, GOR, that express UBE2O at high level by genomic amplification. We are now establishing pleura-specific knock-in mouse of UBE2O in order to identify the effects of this gene amplification frequently occuring in MM.
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| Academic Significance and Societal Importance of the Research Achievements |
UBE2O遺伝子はE2/E3 hybrid ubiquitin-protein ligaseであり、そのユビキチン化基質は多数報告される。結果、UBE2Oの機能は多彩で細胞種により報告が異なる。悪性中皮腫とUBE2O遺伝子増幅に関する報告はなく、その意義も明らかではない。中皮特異的UBE2Oノックインマウスを用いた研究により、悪性中皮腫発症・進展への寄与が明らかになれば、その阻害剤が治療法の開発につながる可能性がある。
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Report
(4 results)
Research Products
(6 results)
