| Project/Area Number |
18K09504
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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 57010:Oral biological science-related
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| Research Institution | Niigata University |
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Principal Investigator |
Saeki Makio 新潟大学, 医歯学系, 教授 (30273692)
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| Co-Investigator(Kenkyū-buntansha) |
山崎 学 新潟大学, 医歯学系, 助教 (10547516)
柿原 嘉人 新潟大学, 医歯学系, 助教 (40379938)
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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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | R2TP / p53 / 口腔扁平上皮がん / Reptin / Pontin / ノックアウトマウス / セツキシマブ |
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| Outline of Final Research Achievements |
R2TP/PAQosome (particle for arrangement of quaternary structure) is a novel multisubunit chaperone specialized in the assembly/maturation of protein complexes that are involved in essential cellular processes such as PIKKs (phosphatidylinositol 3-kinase-like kinases) signaling, snoRNP (small nucleolar ribonucleoprotein) biogenesis, and RNAP II (RNA polymerase II) complex formation. In this review article, we describe the current understanding of R2TP/PAQosome functions and characteristics as well as how the chaperone complex is involved in oncogenesis, highlighting DNA damage response, mTOR (mammalian target of rapamycin) pathway as well as snoRNP biogenesis. Also, we discuss its possible involvement in HNSCC (head and neck squamous cell carcinoma) including OSCC (oral squamous cell carcinoma). Finally, we provide an overview of current anti-cancer drug development efforts targeting R2TP/PAQosome.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、申請者がこれまでに蓄積してきたPontin/Reptinの基礎的な機能解析結果に基づくものである。口腔がんにおいては未だPontin/Reptinの作用機序に関する研究報告例はなかった。申請者はPontin/Reptinが、口腔扁平上皮癌組織の悪性領域で高発現していることを確認し、口腔がんの診断マーカーとなりうることを見出した。Pontin/Reptinは酵母からヒトまでの真核生物において広く保存され、重要な生物学的意味を持つ。これらの基礎的な特性を明らかにすることにより、これまで難治性だった口腔がんはもちろん、他のがん研究への波及効果を含め、他分野へも広く知見を提供できるであろう。
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