Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
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.
Macůrek
Libor
L
Department of Medical Oncology, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands.
Lindqvist
Arne
A
Lim
Dan
D
Lampson
Michael A
MA
Klompmaker
Rob
R
Freire
Raimundo
R
Clouin
Christophe
C
Taylor
Stephen S
SS
Yaffe
Michael B
MB
Medema
René H
RH
D064096:Aurora Kinase A; D064127:Aurora Kinases; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D004789:Enzyme Activation; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000097869:Polo-Like Kinase 1
D064096:Aurora Kinase A; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D010769:Phosphothreonine; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C528235:bora protein, human; C576917:AURKA protein, human