Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos

The Journal of Cell Biology
Nicolas TavernierLionel Pintard

Abstract

The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho-SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing.

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Citations

Jul 28, 2015·Experimental Cell Research·N TavernierL Pintard
Jan 19, 2016·Frontiers in Oncology·Italia Anna AsteritiGiulia Guarguaglini
Nov 11, 2016·Cell Cycle·Alfonso ParrillaAnna Santamaria
Jun 4, 2015·Cell Cycle·Nicolas TavernierLionel Pintard
Feb 8, 2020·EMBO Reports·Mario Aguilar-AragonBarry J Thompson
Oct 17, 2015·Oncotarget·Claire F AspinallStephen S Taylor
Nov 20, 2016·Molecular & Cellular Oncology·Luca CirilloMonica Gotta
Aug 16, 2018·Science Signaling·Vladimir Joukov, Arcangela De Nicolo
Aug 24, 2018·Open Biology·Lionel Pintard, Vincent Archambault
Mar 9, 2019·Genetics·Edward T Kipreos, Sander van den Heuvel
Jun 22, 2016·The Journal of Biological Chemistry·Hee Jin ChungChang-Young Jang
Jan 7, 2021·Life Science Alliance·Helena Silva CascalesArne Lindqvist
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Amelia J Kim, Erik E Griffin
Jun 8, 2017·Cell Reports·Lilia GheghianiOlivier Gavet

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Methods Mentioned

BETA
immunoprecipitation
pull-down
Kinase
pull-downs
gel filtration
two-hybrid
coimmunoprecipitation
transgenic

Software Mentioned

PRALINE
RS
Leica
Percolator
ChromoTek
Mascot
Phospho
LAS AF
Proteome Discoverer

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