| Project/Area Number |
18K06232
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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 44010:Cell biology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
Hikasa Hiroki 産業医科大学, 医学部, 准教授 (40596839)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Hippo経路 / YAP/TAZの制御機構 / 恒常性の破綻 / 炎症性シグナル / Hippo経路エフェクター / YAP/TAZ制御因子 / 生体恒常性の破綻 / Wnt経路 / スクリーニングシステムの開発 / YAP/TAZ制御因子の同定 / 作用点の解析 |
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| Outline of Final Research Achievements |
Hippo pathway effectors YAP/TAZ are under the strict control to maintain biological homeostasis in vivo and are involved in both tumorigenesis and tissue regeneration. In order obtain clues to address how the homeostasis breakdown begins and proceeds, we carried out the systematic screening to search for YAP/TAZ-regulating factors and identified potassium ionophores, a ER-stress inducer, genotoxic molecules, Jak3 inhibitors and several signaling kinases as novel modulators of YAP/TAZ activity, suggesting that YAP/TAZ are regulated by multiple cellular cues.
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| Academic Significance and Societal Importance of the Research Achievements |
YAP/TAZはヒトの多様ながんにおいて機能亢進や過剰発現が確認されおり、腫瘍化や悪性化の原因となっている。だが一方で、YAP/TAZは損傷した組織の修復にも必要であり、人為的にYAP/TAZを損傷組織に活性化させるとより再生が改善され、iPS細胞の誘導にも寄与することがわかっている。本研究により同定されたYAP/TAZ活性化因子はiPS細胞誘導の最適化や、損傷組織の再生医療薬の開発への貢献が期待でき、YAP/TAZ抑制因子は抗がん剤開発の糸口になる可能性がある。
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