Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery

Cell division: PLK1 and aurora A at the checkpoint Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process. Here, activation of PLK1 is shown to occur before mitosis and to depend on phosphorylation by aurora-A kinase, facilitated by a cofactor Bora. The initial activation of PLK1 seems to be a primary function of aurora-A. Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process. Activation of PLK1 is shown to occur before mitosis and to depend on phosphorylation by aurora-A kinase, facilitated by a cofactor Bora. The initial activation of PLK1 seems to be a primary function of aurora-A. Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process 1 . Activation of PLK1 requires phosphorylation of a conserved threonine residue (Thr 210) in the T-loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified 2 , 3 , 4 , 5 , 6 . Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A (AURKA, also known as STK6)-dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora (also known as C13orf34 and FLJ22624), a known cofactor for aurora A (ref. 7 ). We show that Bora/aurora-A-dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint-dependent arrest. Importantly, expression of a PLK1-T210D phospho-mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.