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

Oren Feine, Elvira Hukasova, Wytse Bruinsma, Raimundo Freire, Abraham Fainsod, Julian Gannon, Hiro M. Mahbubani, Arne Lindqvist, Michael Brandeis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)1727-1736
Number of pages10
JournalCell Cycle
Volume13
Issue number11
DOIs
StatePublished - 1 Jun 2014

Bibliographical note

Funding Information:
We would like to thank Tim Hunt (Cancer Research UK) for the generous supply of embryonic extracts and antibodies that enabled this project and for many fruitful discussions. We thank Libor Macurek for cloning of GFP-hBora. We further thank Bela Novak for critical reading of the manuscript and for very helpful comments. This project was funded by a grant from the Israel Science foundation (ISF 345/07). E.H. and A.L. were funded by the Swedish research council, the Swedish cancer foundation, the Swedish childhood cancer foundation and the Swedish foundation for strategic research.

Keywords

  • Bora
  • Cdk1
  • Cell cycle
  • Cleavage
  • Plk1/Plx1

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