Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms2879
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science and from the Ministry of Education, Science, Technology, Sports and Culture of Japan
- Ministry of Health and Welfare, Japan
- Uehara Memorial Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Naito Foundation
- Daiichi-Sankyo Foundation of Life Science
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [24113001, 24590396, 24113005, 24510320, 24659659, 25460089, 23247035] Funding Source: KAKEN
Ask authors/readers for more resources
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 14-3-3 gamma, and this interaction stimulates the catalytic activity of Plk1. Knockdown of 14-3-3 gamma 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 14-3-3 gamma following Plk1-Ser99 phosphorylation downstream of the PI3K-Akt signalling pathway. This novel Plk1 activation pathway controls proper progression from metaphase to anaphase.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available