Signal transduction by centrosome-associated protein kinases

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590396
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: GOTO Hidemasa 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20393126)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 分裂期 / キナーゼ / Plk1 / 14-3-3 / PI3キナーゼ / Akt

Outline of Final Research Achievements

Polo-like kinase 1 (Plk1) controls multiple aspects of mitosis. Here, we identified Ser99 on Plk1 as a novel mitosis-specific phosphorylation site. Plk1-Ser99 phosphorylation creates a docking site for 14-3-3gamma and this interaction stimulates the catalytic activity of Plk1. 14-3-3gamma knockdown or replacement of wild-type Plk1 by a Ser99-phospho-blocking mutant leads to a prometaphase/metaphase-like arrest due to the activation of the spindle assembly checkpoint. Inhibition of PI3K and Akt significantly reduces the level of Plk1-Ser99 phosphorylation and delays metaphase to anaphase transition. Mitotic Plk1 activity is regulated by Plk1 binding to 14-3-3gamma following Plk1-Ser99 phosphorylation downstream of the PI3K-Akt signalling pathway. This novel Plk1 activation pathway controls proper progression from metaphase to anaphase. Our study paves the way for future studies elucidating the relationship between PI3K-Akt pathway and Plk1 in carcinogenesis.

Free Research Field

分子病態学、生化学、細胞生物学