PI 3-kinase-dependent phosphorylation of Plk1–Ser99 promotes association with 14-3-3γ and is required for metaphase–anaphase transition

Kousuke Kasahara, Hidemasa Goto, Ichiro Izawa, Tohru Kiyono, Nobumoto Watanabe, Sabine Elowe, Erich A Nigg and Masaki Inagaki ()
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Kousuke Kasahara: Aichi Cancer Center Research Institute
Hidemasa Goto: Aichi Cancer Center Research Institute
Ichiro Izawa: Aichi Cancer Center Research Institute
Tohru Kiyono: National Cancer Center Research Institute
Nobumoto Watanabe: Chemical Library Validation Team, RIKEN Advanced Science Institute (ASI), 2-1, Hirosawa
Sabine Elowe: Centre de Recherche du CHUQ, 2705 Boulevard Laurier, RC-9800, Quebec City, Québec, Canada G1V 4G2
Erich A Nigg: Biozentrum, University of Basel, Klingelbergstrasse 50/70
Masaki Inagaki: Aichi Cancer Center Research Institute

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Polo-like kinase 1 (Plk1) controls multiple aspects of mitosis and is activated through its phosphorylation at Thr210. Here we identify Ser99 on Plk1 as a novel mitosis-specific phosphorylation site, which operates independently of Plk1–Thr210 phosphorylation. Plk1–Ser99 phosphorylation creates a docking site for 14-3-3γ, and this interaction stimulates the catalytic activity of Plk1. Knockdown of 14-3-3γ or replacement of wild-type (WT) 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 phosphatidylinositol 3-kinase (PI3K) and Akt significantly reduces the level of Plk1–Ser99 phosphorylation and delays metaphase to anaphase transition. Plk1–Ser99 phosphorylation requires not only Akt activity but also protein(s) associated with Plk1 in a mitosis-specific manner. Therefore, mitotic Plk1 activity is regulated not only by Plk1–Thr210 phosphorylation, but also by Plk1 binding to 14-3-3γ following Plk1–Ser99 phosphorylation downstream of the PI3K–Akt signalling pathway. This novel Plk1 activation pathway controls proper progression from metaphase to anaphase.

Date: 2013
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DOI: 10.1038/ncomms2879

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