Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells.

Yann Thomas (1) , Luca Cirillo (2) , Costanza Panbianco (2) , Lisa Martino (1) , Nicolas Tavernier (1) , Françoise Schwager (2) , Lucie van Hove (1) , Nicolas Joly (1) , Anna Santamaria (3) , Lionel Pintard (1) , Monica Gotta (4, 2)

1 IJM (UMR_7592) - Institut Jacques Monod
2 Department of Cellular Physiology and Metabolism
3 Cell Cycle and Ovarian Cancer Group, Spain
4 NCCR-Chemical Biology - Swiss National Centre for Competence in Research Programme Chemical Biology

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.

Domaines: Biologie cellulaire; Biologie du développement

Yann Thomas, Luca Cirillo, Costanza Panbianco, Lisa Martino, Nicolas Tavernier, et al.. Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells.. Cell Reports, 2016, 15 (3), pp.510-8. ⟨10.1016/j.celrep.2016.03.049⟩. ⟨hal-01308307⟩