2016 Fiscal Year Final Research Report
Elucidation of novel mechanisms of signal transduction by retinoic acid via epigenetic regulation and its applications
| Project/Area Number |
26460079
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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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| Research Field |
Biological pharmacy
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| Research Institution | Hoshi 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 | レチノイン酸 / レチノイル化 / 遺伝子発現制御 / 蛋白質修飾 / プロテインキナーゼA / シグナル伝達 / 癌 / 細胞分化 |
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| Outline of Final Research Achievements |
Retinoic acid (RA) elicits a wide variety of biological actions that are important for the living body. It has attracted considerable attention from the viewpoint of prevention and treatment of cancers and lifestyle-related diseases. Using human promyelocytic leukemia cells, this study identified retinoylation (protein modification by RA) as a new mechanism of RA action that is distinct from its actions through the nuclear receptor. A new retinoylated protein was identified as RhoGDI, which controls actin polymerization. In addition, the physiological role of retinoylated protein kinase A (PKA) was elucidated. It was found that PKA is stabilized and transferred into nuclei by RA treatment, where the movement of nuclear histones is also changed. This suggests that RA influences histone modification and effects epigenetic regulation. Novel RA mechanisms were analyzed by identifying nuclear phosphorylated proteins and by clarifying its association with protein modification.
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| Free Research Field |
生化学
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