Development of a novel method to specifically and artificially degrade irregularly post-translationally modified disease-related proteins in cells
| Project/Area Number |
18K19308
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Torigoe Hidetaka 東京理科大学, 理学部第一部応用化学科, 教授 (80227678)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 異常翻訳後修飾蛋白質 / 疾患関連 / シャペロン介在性オートファジー / SUMO化 / SENP2 / Hsc70 / 翻訳後修飾 / 癌抑制蛋白質p53 / p53抑制蛋白質MDM2 / 疾患発症抑制 / 細胞内蛋白質分解 |
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| Outline of Final Research Achievements |
The sumoylated MDM2 more largely expressed in cancer cells than in normal cells promoted the p53 degradation, which resulted in cancer progression. In this study, the plasmid to express fusion proteins consisting of SENP2 to specifically bind to sumoylated MDM2 and Hsc70bm to specifically bind to chaperone-mediated autophagy related Hsc70 was transfected into mammalian cells. Upon the transfection, the complex composed of sumoylated MDM2 and SENP2-Hsc70bm fusion protein and Hsc70 was transferred to the lysosome by chaperone-mediated autophagy, and the sumoylated MDM2 was significantly degraded in the lysosome without the p53 degradation. However, upon the transfection of the SENP2-Hsc70bm expression plasmid into tumor cells of mouse, the sumoylated MDM2 was degraded in a low level with the p53 degradation.
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| Academic Significance and Societal Importance of the Research Achievements |
蛋白質の翻訳後修飾が破綻した異常翻訳後修飾は、細胞内シグナル伝達や細胞機能で異常を引き起こし、疾患発症と関連することが多く、異常翻訳後修飾蛋白質が原因である多くの疾患が見出されている。異常翻訳後修飾蛋白質が特異的に結合する配列と、Hsc70が特異的に結合する配列の融合蛋白質を発現するプラスミドを細胞に導入し、異常翻訳後修飾蛋白質を特異的に人工的に細胞内で分解する新規手法の開発に、本研究成果は端緒を与えた。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] Resveratrol and Its Related Polyphenols Contribute to the Maintenance of Genome Stability2020
Author(s)
Matsuno, Y., Atsumi, Y., Alauddin, M., Rana, M.M., Fujimori, H., Hyodo, M., Shimizu, A., Ikuta, T., Tani, H., Torigoe, H., Nakatsu, Y., Tsuzuki, T., Komai, M., Shirakawa, H., Yoshioka, K.
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Journal Title
Sci.Rep.
Volume: 10
Issue: 1
Pages: 5388-5388
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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