The crosstalk between growth signals and mitotic signals

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Aichi Cancer Center Research Institute
• 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)
• 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
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 細胞周期 / 中心体 / リン酸化 / ユビキチン化

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.

Free Research Field

分子生物学