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

TitlePolo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
Publication TypeJournal Article
Year of Publication2008
AuthorsMacůrek, L, Lindqvist, A, Lim, D, Lampson, MA, Klompmaker, R, Freire, R, Clouin, C, Taylor, SS, Yaffe, MB, Medema, RH
Date Published2008 Sep 4
KeywordsCell Cycle, Cell Cycle Proteins, Cell Line, DNA Damage, Enzyme Activation, Humans, Mitosis, Molecular Sequence Data, Phosphorylation, Phosphothreonine, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Time Factors

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.

Alternate JournalNature
PubMed ID18615013
Grant ListCA112967 / CA / NCI NIH HHS / United States
GM-60594 / GM / NIGMS NIH HHS / United States