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 |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Hoshi University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
今井 正彦 星薬科大学, 薬学部, 助教 (40507670)
高橋 勝彦 星薬科大学, 薬学部, 准教授 (80307066)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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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 / 遺伝子発現調節 / タンパク質修飾 |
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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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Protein kinase A activation by retinoic acid in the nuclei of HL60 cells.2017
Author(s)
Sakai, A., Imai, M., Takahashi, K., Hasegawa, S., Yamasaki, M., Ohba, T., and Takahashi, N.
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Journal Title
Biochim. Biophys. Acta.
Volume: 1861
Issue: 2
Pages: 276-285
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Effects of Pre- and Post-Administration of Vitamin A on the Growth of Refractory Cancers in Xenograft Mice2017
Author(s)
Li, C., Imai, M., Yamasaki, M., Hasegawa, S., and Takahashi, N.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 40
Issue: 4
Pages: 486-494
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action2017
Author(s)
Li, C., Imai, M., Hasegawa, S., Yamasaki, M., and Takahashi, N.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 40
Issue: 4
Pages: 495-503
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Retinoylation (covalent modification by retinoic acid) of Rho-GDIβ in the human myeloid leukemia cell line HL60 and its functional significance.2016
Author(s)
Takahashi, N., Ohba, T., Imai, M., Hasegawa, S., Takahashi, K., Yamasaki, M., and Kameoka, Y.
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Journal Title
Biochim. Biophys. Acta.
Volume: 1861
Issue: 12
Pages: 22011-2019
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation2015
Author(s)
M. Imai, T. Kumaoka, M. Hosaka, Y. Sato, C. Li, M. Sudoh, Y. Tamada, H. Yokoe, S. Saito, M. Tsubuki, N. Takahashi
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Journal Title
Bioorganic & Medicinal Chemistry
Volume: 23
Issue: 13
Pages: 3788-3795
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Effects of retinoids on refractory cancers2015
Author(s)
Chuan Li, Masahiko Imai, and Noriko Takahashi
Organizer
The 3rd International Conference on Retinoids, The 26th Congress of the Japanese Society for Retinoid Research
Place of Presentation
Gifu, Japan
Year and Date
2015-10-21
Related Report
Int'l Joint Research
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[Presentation] チロシナーゼ活性阻害剤の探索2014
Author(s)
高橋典子、今井正彦、小森悠
Organizer
フォーラム2014:衛生薬学・環境トキシコロジー
Place of Presentation
筑波
Year and Date
2014-09-19 – 2014-09-20
Related Report
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