| Project/Area Number |
18K15042
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 中心体 / 染色体不安定性 / 発癌 / 中心体複製 / 繊毛病 / 男性不妊 / 発育不全 / 不妊 / 中心小体 / PCM / PLK4 / 母中心小体 / シグナル伝達 / 染色体安定性 / 数理解析 / 小頭症 / 抗癌剤 / 中心体過剰複製 |
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| Outline of Final Research Achievements |
Centrosomes serve as the microtubule-organizing centers responsible for mitotic spindle formation and chromosome segregation. Hence centrosome amplification causes erroneous kinetochore-microtubule attachment, thereby promoting chromosome missegregation. Indeed various cancer cells have extra centrosomes, suggesting that the numerical aberration of centrosomes increase the risk of tumorigenesis. Therefore, centriole duplication is strictly regulated to once per cell cycle, but the molecular mechanism is not fully understood.
We have tried to elucidate that mechanism and found the region required for the recruitment to centrosomes. In addition, we identified several proteins involved in centrosome localization by performing mass spectrometry-based screening. Furthermore, we utilized the molecular basis of centrosome localization and identified some seed compounds that can be promising agent for cancer therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
中心体の構造的・機能的異常は発癌リスクを高めるだけでなく、繊毛病または男性不妊等の主要因となる。このため中心体の機能およびその複製機構を明らかにすることは上記疾患の病態メカニズムの解明にも繋がる。そこで本研究では中心体複製期に起こる中心体複製制御分子の中心体移行機構の解明を目指して実験を実施し、同機構の根底になる基本原理を解明することに成功した。更にこの基本原理を利用することで抗癌剤として有望なシード化合物の同定にも成功した。
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