2016 Fiscal Year Final Research Report
Development of a bio-imaging system for mechanistic assessment of the nucleolar stress response and construction of novel technology for therapeutics
| Project/Area Number |
26670160
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 核小体 / 細胞分裂 / p53 / 核小体ストレス応答 / 蛍光レポーター / 創薬スクリーニング |
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| Outline of Final Research Achievements |
The nucleolus is disorganized at mitosis and reassembled at the beginning of interphase. Nucleolar stress response is a maintenance mechanism for nucleolar homeostasis to induce TP53 dependent growth inhibition during the nucleolar abnormality. However physiological relevance between mitotic nucleolar disassembly/assembly and nucleolar stress response is unknown. We developed a fluorescent reporter system and found mitotic inhibitors as a novel nucleolar stress inducer by chemical screening. Mitotic abnormality by inhibitors of mitosis increased p53 protein and inhibited cancerous cell growth on Nucleolar stress response dependent manner. Taken together, our results provide Nucleolar stress response as a novel mitotic surveillance mechanism depend on nucleolar reassembly. These results also suggested that our reporter system might enable to identified novel cancer therapeutics utilizing the nucleolar stress.
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| Free Research Field |
分子腫瘍学
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