| Project/Area Number |
25460089
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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 |
Biological pharmacy
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
Kasahara Kousuke 愛知県がんセンター(研究所), 腫瘍医化学部, 研究員 (90455535)
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| Research Collaborator |
TANAKA Hiroki 愛知県がんセンター(研究所), 腫瘍医化学部, リサーチレジデント
KAWAMOTO Eriko 愛知県がんセンター(研究所), 腫瘍医化学部, 嘱託技師
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 細胞周期 / 中心体 / リン酸化 / ユビキチン化 / 増殖生存シグナル / 一次繊毛 / 細胞分裂 / 細胞分裂期 / Plk1キナーゼ / PI3キナーゼ / Aktキナーゼ / 14-3-3 |
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| Outline of Final Research Achievements |
In this study, we have revealed that PI3-kinase-Akt/PKB signaling pathway is essential for proper mitotic progression. In mitosis, Akt kinase activity is responsible for Plk1 (Polo-like kinase 1) phosphorylation at Ser-99. This phosphorylation creates the docking site of 14-3-3 gamma and elevates the Plk1 kinase activity, thereby regulating the metaphase-anaphase transition.
We further show that ubiquitin-proteasome system controls primary cilia formation. In response to serum starvation, the ubiquitin E3 ligase CRL3-KCTD17 induces polyubiqutination-dependent degradation of trichoplein, one of the most important negative regulator of ciliogenesis. The trichoplein degradation attenuates the kinase activity of Aurora A, and thereby triggers ciliogenesis.
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