Project/Area Number |
17K17739
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Neurosurgery
Pathological medical chemistry
|
Research Institution | Niigata University |
Principal Investigator |
Masayasu Okada 新潟大学, 医歯学総合病院, 助教 (00626492)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 膠芽腫 / GAP-43 / 神経成長因子 / リン酸化 / プロテオーム解析 / Glioblastoma / phosphorylation / glioblastoma / シグナル伝達 |
Outline of Final Research Achievements |
The therapeutic application from the viewpoint of controlling the nerve growth-related protein-43kDa (GAP-43) itself, which is involved in cell projection formation and treatment resistance in glioblastoma, which is the most intractable malignant brain tumor, has not been elucidated. I identified novel phosphorylation sites of GAP-43 by performing a phosphoproteome analysis by human glioblastoma excised specimen. I also found the kinase responsible for the novel phosphorylation site of GAP-43 in human is JNK, as well as in rodents. This study presents the first step forwards to the development of a new approach to glioblastoma treatment focusing on control of phosphorylation of GAP-43.
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Academic Significance and Societal Importance of the Research Achievements |
研究代表者は、五十嵐道弘教授(新潟大学大学院医歯学系神経生化学分野)らとともに、げっ歯類の神経細胞の軸索伸長時に活性化するGAP-43の新規リン酸化部位(セリン(S)96とトレオニン(T)172)とそのリン酸化キナーゼがJNKであることを2018年のiSceince誌に報告し、停滞していたGAP-43研究を前進させた。本研究は、ヒト膠芽腫に発現するGAP-43においても、齧歯類と相同性のある配列がリン酸化し、そのキナーゼがJNKであることを確認した。この結果は、ヒトのGAP-43の理解を深め、GAP-43のリン酸化制御の観点で膠芽腫の新規治療法の基盤となる重要な発見である。
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