| Project/Area Number |
17K14984
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kikuchi Ippei 東京大学, 大学院医学系研究科(医学部), 特任研究員 (80772376)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | がん / シグナル伝達 / リン酸化 / Hippoシグナル / ゲノム編集 / クロストーク / parafibromin |
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| Outline of Final Research Achievements |
Recent studies have indicated that a nuclear protein Parafibromin integrates the transcriptional outputs of multiple cancer-related signaling pathways such as Wnt, Hedgehog, and Notch signaling. In the present study, we found that increased tyrosine dephosphorylation of Parafibromin in cells leads to mitotic defects, thereby resulting in the decreased cell growth. We also demonstrated that Parafibromin forms a protein complex with YAP and TAZ,thereby promoting the transcriptional activation of Hippo signal target genes. Furthermore, we succeeded in establishing the new genetically engineered mouse model in which the multiple tyrosine kinases responsible for Parafibromin phosphorylation are simultaneously deleted.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、様々ながん種において細胞のがん化を促進する因子として近年大きな注目を集めるYAP・TAZタンパク質の機能制御にParafibrominならびにそのチロシンリン酸化が重要な役割を果たすことを世界に先駆けて明らかにした。本研究成果に基づいてParafibromin-YAP・TAZ複合体形成を阻害する薬剤などをスクリーニングすることで、これまで有効な治療法が確立されていないがんに対する新たな治療法の開発に繋がることが期待できる。
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