| Project/Area Number |
24300328
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MIKI Yoshio 東京医科歯科大学, 難治疾患研究所, 教授 (10281594)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Akira 東京医科歯科大学, 難治疾患研究所, 准教授 (50321790)
TAKENAKA Katsuya 東京医科歯科大学, 難治疾患研究所, 助教 (20378706)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 乳がん / BRCA2 / 合成致死 / 化合物ライブラリー / BRCA1/2遺伝子 / がん抑制遺伝子 / BRCA1/BRCA2 / 抗がん剤 |
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| Outline of Final Research Achievements |
We have reported the potential synthetic lethality relationships between BRCA2 deficiency and paclitaxel (PTX). To date, PTX treatment of BRCA2-siRNA knockdown cells has been found to result in a significant increase in microtubule polymer mass. To investigate whether the BRCA2 protein forms the microtubule cytoskeleton complex, we performed immunoprecipitation experiments using anti-BRCA2 antibody. Analysis of the immunoprecipitate by mass spectrometry identified the microtubule-associated proteins (MAP2, MAP4, and Tau) that directly bind microtubules to promote microtubule stabilization. Furthermore, a cell-based tubulin polymerization assay following the treatment of the siRNA knockdown of BRCA2 revealed microtubule stabilization by the effect of MAP4. In this study, we identified MAP4 as a new binding partner of BRCA2, suggesting that a synergistic effect of PTX and MAP4 on tubulin assembly contributes to microtubule stabilization.
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