Dysregulation of stress signaling leading to oncogenesis by NDRG2-deficicency
| Project/Area Number |
17H03581
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
尾野 雅哉 国立研究開発法人国立がん研究センター, 研究所, 研究員 (00270900)
中畑 新吾 宮崎大学, 医学部, 准教授 (80437938)
市川 朝永 宮崎大学, 医学部, 助教 (80586230)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | ATL / HTLV-1 / NDRG2 / PRMT5 / HSP90 / アルギニンメチル化 / PP2A / sythethic lethality / HTLV1 / client protein / 癌 / 感染症 |
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| Outline of Final Research Achievements |
We have identified a novel PTEN-binding NDRG2 tumor suppressor gene from the genome analysis of adult T-cell leukemia Isolated as a protein and used for the regulation of PTEN activity by PP2A-mediated dephosphorylation of PTEN NDRG2 has been implicated in the pathogenesis of multiple cancers and has been shown to play a key role in the development of new HSP 90/PRMT5 complex. In particular, down-regulation of PRMT5 expression caused HSP90 dysfunction in ATL/cancer cells and reduced AKT The degradation and apoptosis of many Client proteins, including NDRG2 Therefore, NDRG2-deficient cancer cells show abnormalities in phosphorylation and arginine methylation, and cancer cells It is suggested that this is associated with a specific increase in HSP90 activity.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究ではNDRG2癌抑制遺伝子機能異常を中心に研究を行っており、NDRG2異常をきたす癌・白血病におけるタンパク質リン酸化、メチル化修飾異常を網羅的に明らかしている。、その中心として新たながん細胞特異的HSP90の新規活性調節機構としてPRMT5によるアルギニンメチル化を同定した。この発癌機構を基礎とした新規治療薬の開発へつながる重要な研究である。
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Report
(4 results)
Research Products
(42 results)
