Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells

Genes Cells. 2002 Nov;7(11):1173-82. doi: 10.1046/j.1365-2443.2002.00592.x.

Abstract

Background: Various mitotic events are controlled by Cdc2-cyclin B and other mitotic kinases. Aurora/Ipl1-related mitotic kinases were proved to play key roles in mitotic progression in diverse lower organisms. Aurora-A is a mammalian counterpart of aurora/Ipl1-related kinases and is thought to be a potential oncogene. However, the regulation of aurora-A activation and the commitment of aurora-A in the progression of G2-M phase are largely unknown in mammalian cells.

Results: We demonstrated that aurora-A is activated depending on the activation of Cdc2-cyclin B in mammalian cells. Since Cdc2-cyclin B does not directly phosphorylate aurora-A, indirect pathways such as the inhibition of PP1 by Cdc2-cyclin B may act for the activation of aurora-A kinase. Microinjection of anti-aurora-A antibodies into HeLa cells at late G2 phase caused a significant delay in mitotic entry. Furthermore, aurora-A activation at G2-M transition was inhibited by DNA damage, and the over-expression of aurora-A induced the abrogation of the DNA damage-induced G2 checkpoint.

Conclusions: Aurora-A is activated downstream of Cdc2-cyclin B and plays crucial roles in proper mitotic entry and G2 checkpoint control. Dysregulation of aurora-A induces abnormal G2-M transition in mammalian cells and may lead to chromosome instability, which results in the development and progression of malignant tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Aurora Kinase A
  • Aurora Kinases
  • Cell Cycle Proteins
  • Cyclin B1
  • Cyclin-Dependent Kinases / physiology
  • Enzyme Activation / physiology
  • G2 Phase / physiology*
  • HeLa Cells
  • Humans
  • Mitosis / physiology*
  • Phosphorylation
  • Protein Kinases / immunology
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases
  • Rats
  • Xenopus Proteins

Substances

  • Antibodies
  • Cell Cycle Proteins
  • Cyclin B1
  • Xenopus Proteins
  • Protein Kinases
  • AURKA protein, Xenopus
  • Aurka protein, rat
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases