Bora, CEP192 and Cenexin regulate distinct Plk1-dependent cell and centrosome cycle transitions

Polo-like kinase 1 (Plk1) regulates multiple steps of the cell and centrosome cycle, including mitotic entry, DNA-damage recovery, centrosome maturation and centriole disengagement. Plk1 activity depends on several independent cofactors, such as the cytoplasmic Bora, and the centrosomal proteins Cep192 and Cenexin. However, whether these Plk1 coactivators differentially regulate the Plk1-dependent processes is unknown. Here, we show that each Plk1 coactivator controls different cell and centrosome cycle transitions in human cells. We find that Plk1 already acts in S-phase, where under the control of Cep192 and Aurora A it promotes replication origin firing. Bora is the main Plk1 activator driving mitotic entry, DNA-damage recovery and centrosome maturation in G2, while centriole disengagement is mainly regulated by Cep192 and Cenexin. Our results thus uncover a complex Plk1 activation regulatory network, in which distinct upstream activators dictate its activity in a context-dependent manner.