Comprehensive analysis of p53 negative regulation by novel oncogene GRWD1
| Project/Area Number |
18K07201
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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 50010:Tumor biology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | GRWD1 / p53 / がん / RPS17 / p21 / TCGA / FAIRE / RPL22 / MDM2 / RPs |
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| Outline of Final Research Achievements |
We have previously reported that GRWD1 binds to the tumor-suppressive ribosomal proteins RPL11 or RPL23 and inhibits the function. Consequently, GRWD1 suppresses p53 and functions as an oncogene. In this study, we found that GRWD1 directly regulates the transcriptional activity of p53. Furthermore, we focused on the ribosomal protein RPS17, whose GRWD1 binding was identified by the previous mass spectrometry analysis, and examined whether RPS17 has tumor suppressive activity. As a result, we found that RPS17 functions as a tumor suppressor by a regulating the localization of nucleolar factor nucleophosmin.
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| Academic Significance and Societal Importance of the Research Achievements |
がん細胞ではp53の変異が認められることが多いが、その一方で、p53に異常のないがん患者も多く存在する。本研究により、GRWD1が多様な経路によってp53を負に制御することにより、細胞のがん化を促進させることを明らかにした。また、TCGAデータベースを用いた解析により、いくつかのがん種において、GRWD1タンパク質量の増加はがんの悪性度を上昇させ、予後不良の予測因子となり得ることも発見した。よって、GRWD1発現検査はがん治療方針のより適切な決定につながる可能性がある。さらに、本研究は幅広いがんの病態把握やGRWD1を標的とする新たな抗がん剤開発の一助となることも期待できる。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10.2019
Author(s)
Yokoyama T., Yukuhiro M., Iwasaki Y., Tanaka C., Sankoda K., Fujiwara R., Shibuta A., Higashi T., Motoyama K., Arima H., Yoshida K., Sugimoto N., Morimoto H., Kosako H., Ohshima T. and Fujita M.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibiting the MCM8-9 complex selectively sensitizes cancer cells to cisplatin and olaparib.2019
Author(s)
Morii, I., Iwabuchi, Y., Mori, S., Suekuni, M., Natsume, T., Yoshida, K., Sugimoto, N., Kanemaki, MT. and Fujita, M.
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Journal Title
Cancer Science
Volume: 110
Issue: 3
Pages: 1044-1053
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Glutamate-rich WD40 repeat containing 1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system.2018
Author(s)
Watanabe, S., Fujiyama, H., Takafuji, T., Kayama, K., Matsumoto, M., Nakayama, KI., Yoshida, K., Sugimoto, N. (Corresponding author), and Fujita, M.
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Journal Title
Journal of Cell Science
Volume: 131
Issue: 15
Pages: 213009-213009
DOI
Related Report
Peer Reviewed / Open Access
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