| Project/Area Number |
18K06966
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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 49010:Pathological biochemistry-related
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| Research Institution | Gunma Paz University |
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Principal Investigator |
Kimura Ayuko 群馬パース大学, 保健科学部, 講師 (50553616)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | プロテアソーム / N-ミリストイル化 / ユビキチン化 / ストレス応答 / プロテオミクス / 癌 / 微小環境ストレス |
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| Outline of Final Research Achievements |
In previous study, authors indicated that N-mirystoylation anchors proteasome within the nucleus and enhances the degradation of various nuclear proteins, resulting in the increased proliferation of budding yeast under various stress conditions such as heat. In addition, the fact that accumulation of nuclear proteasomes was observed with antitumor drug resistance in some cancers under microenvironment stress, and overexpression of N-myristoyl transferase is frequently detected in many cancers prompted us to analyze the biological significance of N-myristoylation in human cancer. Current analysis on the subcellular localization of proteasome and ubiquitin proteome, which use strain carrying mutation in N-myristoylation site of proteasome and some cancer cell lines with high or low expression levels of N-myristoyltransferase, indicated that N-myristoylation controls degradation of various stress response-related proteins via regulation of intracellular localization of proteasomes.
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| Academic Significance and Societal Importance of the Research Achievements |
プロテアソームには多数の翻訳後修飾部位が存在するが、ヒトにおける生理機能についてはほとんど情報がなかった。本研究により、プロテアソームサブユニット中唯一の脂質修飾として知られるN-ミリストイル化が、微小環境ストレスを含むがんのストレス応答に関わる様々なタンパク質の分解に関わる可能性が初めて示唆された。本研究で得られた知見は将来的に、多発性骨髄腫の治療薬であり悪性度の高い膵臓癌などの新規治療薬としても期待される、プロテアソーム阻害剤の作用機序の解明や適用疾患・薬効予測法の探索研究にもつながっていくものと期待される。
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