Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process. 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. 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.

High-quality Ge epilayers on Si with low threading-dislocation densities were achieved by a two-step ultrahigh vacuum/chemical-vapor-deposition process followed by cyclic thermal annealing. On large Si wafers, Ge on Si with threading-dislocation density of 2.3×107 cm−2 was obtained. Combining selective area growth with cyclic thermal annealing produced an average threading-dislocation density of 2.3×106 cm−2.We also demonstrated small mesas of Ge on Si with no threading dislocations. The process described in this letter for making high-quality Ge on Si is uncomplicated and can be easily integrated with standard Si processes.

Plk1 plays a pivotal role in cell proliferation and is considered an attractive target for anti-cancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope-binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interacted with the PBD of Plk1, but not the two closely-related Plk2 and Plk3. Comparative binding studies and analyses of crystal structures of the Plk1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high affinity anchor, whereas the N-terminal residues are critical for providing both specificity and affinity to the interaction. Inhibition of the Plk1 PBD by phospho-Thr mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. Thus, the mode of the minimal peptide and PBD interaction may provide a template for designing anti-Plk1 therapeutic agents.