2020 Fiscal Year Final Research Report
Analysis of molecular mechanisms of cell proliferation in BAP1-mutated cancer using synthetic lethal phenotypes
| Project/Area Number |
18K06979
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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 49010:Pathological biochemistry-related
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| Research Institution | Tokyo University of Technology (2019-2020)
Juntendo University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 合成致死 / 悪性中皮腫 |
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| Outline of Final Research Achievements |
We analyzed USP1 and CHK2 among the genes that showed synthetic lethal phenotype for BAP1 mutation in cultured cells.The following results were obtained. (1) FANCD2, which has been reported as a target protein of the deubiquitinating enzyme USP1, is also deubiquitinated in BAP1 in vitro, (2) knockdown of BAP1 in malignant mesothelioma cell lines delays the S phase, and (3) inhibiting USP1/CHK2 blocks cancer growth in tumor-bearing mice using BAP1 mutant cells.
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| Free Research Field |
がん
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| Academic Significance and Societal Importance of the Research Achievements |
BAP1遺伝子はがん抑制遺伝子であるため、その変異によって起こるがんに対する抗がん剤開発では直接標的にしにくいという問題がある。そこで合成致死表現型を用い、将来的に標的になる可能性がある分子標的の探索をするとともに、候補遺伝子の新しい機能を解析した。
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