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

Publication date: Available online 7 April 2016
Source:Cell Reports
Author(s): Yann Thomas, Luca Cirillo, Costanza Panbianco, Lisa Martino, Nicolas Tavernier, Françoise Schwager, Lucie Van Hove, Nicolas Joly, Anna Santamaria, Lionel Pintard, Monica Gotta
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.

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Teaser

Thomas et al. now find that Cyclin B/Cdk1 phosphorylates SPAT-1/Bora to promote Plk1 activation in C. elegans and in human cells. They identify three conserved phosphorylation sites in SPAT-1 and Bora that promote timely mitotic entry in the embryo and G2-checkpoint recovery from DNA damage in human cells.


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