Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase

FEBS Lett. 2005 Jun 20;579(16):3385-91. doi: 10.1016/j.febslet.2005.04.080.

Abstract

We investigated why treatment of cells with dual aurora A and B kinase inhibitors produces phenotypes identical to inactivation of aurora B. We found that dual aurora kinase inhibitors in fact potently inhibit cellular activities of both kinases, indicating that inactivation of aurora B bypasses aurora A in mitosis. RNAi experiments further established that inactivation of aurora B indeed bypasses the requirement for aurora A and leads to polyploidy. Inactivation of aurora A activates checkpoint kinase BubR1 in an aurora B-dependent manner. Our results thus show that aurora B is responsible for mitotic arrest in the absence of aurora A.

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Benzamides / pharmacology
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Humans
  • Indoles / pharmacology
  • Mitosis / genetics
  • Mitosis / physiology*
  • Polyploidy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Quinazolines / pharmacology
  • RNA Interference
  • Sulfonamides / pharmacology

Substances

  • 4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline
  • Benzamides
  • Cell Cycle Proteins
  • Indoles
  • Protein Kinase Inhibitors
  • Quinazolines
  • Sulfonamides
  • Protein Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • hesperadin