2021 Fiscal Year Final Research Report
Temporal information coding of cell proliferation inhibitory signal revealed by optical measurement and control of p38 activity in living cells
| Project/Area Number |
19K06548
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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 43030:Functional biochemistry-related
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ストレス応答 / 癌細胞 / 増殖抑制 / キナーゼ |
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| Outline of Final Research Achievements |
Human cells have pathways that contribute to growth suppression by induction of cell cycle arrest or cell death. In this study, we focused on growth suppressing stress-activated kinase p38 and proceeded with the development of a novel p38 activity reporter and optogenetic p38 control system for the purpose of understanding the regulatory mechanism of cell-growth suppressing signaling. As a result, I succeeded in constructing a new reporter that enables high-throughput signal detection even under condition without light irradiation. In addition, using this reporter, imaging analysis was performed on colon cancer-derived cells, and the temporal relationship between p38 activity and cell death was found.
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| Free Research Field |
生理学、分子生物学、薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
近年、細胞内情報伝達分子の網羅的な解析技術が進み、増殖抑制に関わる分子の同定は数多く報告されているが、個々の分子が実際に生きた細胞内でどのように振る舞うかはほとんど明らかになっていない。本研究によって、さまざまな細胞種に普遍的に存在するp38分子が細胞死を誘導する際にどのような活性変動をするかを明らかにすることができた。さらに、その動的挙動と細胞機能との関連を解析するのに有用な光遺伝学的活性操作系も新規に構築することができた。これらの知見を活用することで、癌や異常免疫等に対する新たな診断法や治療法開発への応用が期待される。
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