Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells
Yann Thomas,
Luca Cirillo,
Costanza Panbianco,
Lisa Martino,
Nicolas Tavernier,
Françoise Schwager,
Lucie Van Hove,
Nicolas Joly,
Anna Santamaria,
Lionel Pintard,
Monica Gotta
Affiliations
Yann Thomas
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Luca Cirillo
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Costanza Panbianco
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Lisa Martino
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Nicolas Tavernier
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Françoise Schwager
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Lucie Van Hove
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Nicolas Joly
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Anna Santamaria
Cell Cycle and Ovarian Cancer Group, Biomedical Research Unit in Gynecology, Collserola Building, Vall Hebron Research Institute, 08035 Barcelona, Spain
Lionel Pintard
Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France
Monica Gotta
Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
The conserved Bora protein is a Plk1 activator, essential for checkpoint recovery after DNA damage in human cells. Here, we show that Bora interacts with Cyclin B and is phosphorylated by Cyclin B/Cdk1 at several sites. The first 225 amino acids of Bora, which contain two Cyclin binding sites and three conserved phosphorylated residues, are sufficient to promote Plk1 phosphorylation by Aurora A in vitro. Mutating the Cyclin binding sites or the three conserved phosphorylation sites abrogates the ability of the N terminus of Bora to promote Plk1 activation. In human cells, Bora-carrying mutations of the three conserved phosphorylation sites cannot sustain mitotic entry after DNA damage. In C. elegans embryos, mutation of the three conserved phosphorylation sites in SPAT-1, the Bora ortholog, results in a severe mitotic entry delay. Our results reveal a crucial and conserved role of phosphorylation of the N terminus of Bora for Plk1 activation and mitotic entry.
