Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry

Science. 2008 Jun 20;320(5883):1655-8. doi: 10.1126/science.1157425.

Abstract

A central question in the study of cell proliferation is, what controls cell-cycle transitions? Although the accumulation of mitotic cyclins drives the transition from the G2 phase to the M phase in embryonic cells, the trigger for mitotic entry in somatic cells remains unknown. We report that the synergistic action of Bora and the kinase Aurora A (Aur-A) controls the G2-M transition. Bora accumulates in the G2 phase and promotes Aur-A-mediated activation of Polo-like kinase 1 (Plk1), leading to the activation of cyclin-dependent kinase 1 and mitotic entry. Mechanistically, Bora interacts with Plk1 and controls the accessibility of its activation loop for phosphorylation and activation by Aur-A. Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinases
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Enzyme Activation
  • Feedback, Physiological
  • G2 Phase
  • HeLa Cells
  • Humans
  • Kinetics
  • Mitosis*
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Binding
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Xenopus
  • Xenopus Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Xenopus Proteins
  • bora protein, human
  • Aurora Kinases
  • Plk1 protein, Xenopus
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase