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2014 Fiscal Year Final Research Report

Signal transduction by centrosome-associated protein kinases

Research Project

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Project/Area Number 24590396
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionAichi 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

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Published: 2016-06-03  

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