title: Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells.
abstract: 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.
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Thomas
authors.affiliation: Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Cirillo
authors.affiliation: Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Costanza
authors.initials: C
authors.lastname: Panbianco
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Martino
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tavernier
authors.affiliation: Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Françoise
authors.initials: F
authors.lastname: Schwager
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Van Hove
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Joly
authors.affiliation: Cell Cycle and Ovarian Cancer Group, Biomedical Research Unit in Gynecology, Collserola Building, Vall Hebron Research Institute, 08035 Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Santamaria
authors.affiliation: Jacques Monod Institute, UMR7592, Paris-Diderot University, Centre National de la Recherche Scientifique, 75013 Paris, France. Electronic address: lionel.pintard@ijm.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Pintard
authors.affiliation: Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Swiss National Centre for Competence in Research Program Chemical Biology, 1211 Geneva, Switzerland. Electronic address: monica.gotta@unige.ch.
authors.forename: Monica
authors.initials: M
authors.lastname: Gotta
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D019926:Cyclin B / Q000378:metabolism; D004249:DNA Damage; D004625:Embryo, Nonmammalian / Q000166:cytology; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D000596:Amino Acids; D016203:CDC2 Protein Kinase; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C552693:SPAT-1 protein, C elegans; C528235:bora protein, human