Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos.
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.
Jacques Monod Institute, UMR7592; and Mass Spectrometry Facility, Jacques Monod Institute, UMR7592; Paris-Diderot University-Centre National de la Recherche Scientifique, 75013 Paris, France.
Nicolas
N
Tavernier
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva 4, Switzerland.
Anna
A
Noatynska
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva 4, Switzerland.
Costanza
C
Panbianco
Jacques Monod Institute, UMR7592; and Mass Spectrometry Facility, Jacques Monod Institute, UMR7592; Paris-Diderot University-Centre National de la Recherche Scientifique, 75013 Paris, France.
Lisa
L
Martino
Jacques Monod Institute, UMR7592; and Mass Spectrometry Facility, Jacques Monod Institute, UMR7592; Paris-Diderot University-Centre National de la Recherche Scientifique, 75013 Paris, France.
Lucie
L
Van Hove
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva 4, Switzerland.
Françoise
F
Schwager
Jacques Monod Institute, UMR7592; and Mass Spectrometry Facility, Jacques Monod Institute, UMR7592; Paris-Diderot University-Centre National de la Recherche Scientifique, 75013 Paris, France.
Thibaut
T
Léger
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva 4, Switzerland Swiss National Centre for Competence in Research Program Chemical Biology, 1211 Geneva, Switzerland Monica.Gotta@unige.ch pintard.lionel@ijm.univ-paris-diderot.fr.
Monica
M
Gotta
Jacques Monod Institute, UMR7592; and Mass Spectrometry Facility, Jacques Monod Institute, UMR7592; Paris-Diderot University-Centre National de la Recherche Scientifique, 75013 Paris, France Monica.Gotta@unige.ch pintard.lionel@ijm.univ-paris-diderot.fr.
Lionel
L
Pintard
D000595:Amino Acid Sequence; D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007814:Larva / Q000166:cytology / Q000201:enzymology; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D061987:Sf9 Cells; D018411:Spodoptera; D000097869:Polo-Like Kinase 1
D064096:Aurora Kinase A; D016203:CDC2 Protein Kinase; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; C552693:SPAT-1 protein, C elegans; C513017:plk-1 protein, C elegans; D000097869:Polo-Like Kinase 1