| Project/Area Number |
17K11644
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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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| Research Field |
Functional basic dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
Asano Satoshi 広島大学, 医系科学研究科(歯), 助教 (30570535)
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| Co-Investigator(Kenkyū-buntansha) |
兼松 隆 九州大学, 歯学研究院, 教授 (10264053)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 細胞分裂 / 細胞質分裂 / RhoA / OCRL1 / PI(4,5)P2 / ミオシンII / シスプラチン / アポトーシス / 乳癌 / PI3K / AKT / 細胞周期 / 乳がん / 癌 / 細胞移動 / 細胞増殖 |
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| Outline of Final Research Achievements |
Cytokinesis is the last step of cell division that physically separates the daughter cells. Cytokinesis failure contributes to the development of pathologies such as cancer. Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] accumulates at the cleavage furrow and is involved in Rho-type GTPase RhoA-dependent furrow ingression during cytokinesis. Here, we showed that PRIP is required for the localization of PI(4,5)P2 to the cleavage furrow. PRIP knockdown caused abnormal cytokinesis such as a furrow regression and cytokinesis delay. Fluorescence microscopy analysis confirmed weak localization of RhoA and phosphorylated myosin II regulatory light chain (MRLC), which upregulates myosin II motor activity for furrow ingression, in cleavage furrow in HeLa cells reduced PRIP. These results suggest that PRIP is required for stable maintenance of PI(4,5)P2 in the cleavage furrow, which is a prerequisite for the RhoA signaling-dependent progression of cytokinesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、我々が見出し、癌細胞の増殖や転移抑制効果を確認したPRIPの分子機能に着目して、抗腫瘍薬開発を目指す基礎研究である。今回新たにPRIPが細胞質分裂にも関わっていることを明らかにした。正常細胞の細胞質分裂異常によって多核化が起こると、染色体が多倍体化するが、これは癌化の一因であると考えられている。本研究によってPRIPが細胞質分裂の正常化に寄与することと、そのメカニズムが明らかになったことで、癌化や癌の増悪化を抑制するPRIPをターゲットとした抗腫瘍薬の開発に繋がる意義深い研究になったと考える。
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