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Cell Cycle. 2014;13(11):1727-36. doi: 10.4161/cc.28630. Epub 2014 Mar 26.

Phosphorylation-mediated stabilization of Bora in mitosis coordinates Plx1/Plk1 and Cdk1 oscillations.

Author information

1
Department of Genetics; The Hebrew University of Jerusalem; Jerusalem, Israel.
2
Department of Cell and Molecular Biology; Karolinska Institute; Stockholm, Sweden.
3
Department of Cell Biology; The Netherlands Cancer Institute; Amsterdam, Netherlands.
4
Unidad de Investigación; Hospital Universitario de Canarias; Instituto de Tecnologias Biomedicas; Tenerife, Spain.
5
Department of Developmental Biology and Cancer Research; The Hebrew University of Jerusalem; Jerusalem, Israel.
6
Cancer Research UK; Clare Hall Laboratories; South Mimms, Hertfordshire, UK.

Abstract

Cdk1 and Plk1/Plx1 activation leads to their inactivation through negative feedback loops. Cdk1 deactivates itself by activating the APC/C, consequently generating embryonic cell cycle oscillations. APC/C inhibition by the mitotic checkpoint in somatic cells and the cytostatic factor (CSF) in oocytes sustain the mitotic state. Plk1/Plx1 targets its co-activator Bora for degradation, but it remains unclear how embryonic oscillations in Plx1 activity are generated, and how Plk1/Plx1 activity is sustained during mitosis. We show that Plx1-mediated degradation of Bora in interphase generates oscillations in Plx1 activity and is essential for development. In CSF extracts, phosphorylation of Bora on the Cdk consensus site T52 blocks Bora degradation. Upon fertilization, Calcineurin dephosphorylates T52, triggering Plx1 oscillations. Similarly, we find that GFP-Bora is degraded when Plk1 activity spreads to somatic cell cytoplasm before mitosis. Interestingly, GFP-Bora degradation stops upon mitotic entry when Cdk1 activity is high. We hypothesize that Cdk1 controls Bora through an incoherent feedforward loop synchronizing the activities of mitotic kinases.

KEYWORDS:

Bora; Cdk1; Plk1/Plx1; cell cycle; cleavage

PMID:
24675888
PMCID:
PMC4111719
DOI:
10.4161/cc.28630
[Indexed for MEDLINE]
Free PMC Article

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