Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation

Oncogene. 2005 Nov 10;24(49):7266-72. doi: 10.1038/sj.onc.1208884.

Abstract

Aurora-B, previously known as AIM-1, is a conserved eukaryotic mitotic protein kinase. In mammals, this kinase plays an essential role in chromosomal segregation processes, including chromosome condensation, alignment, control of spindle checkpoints, chromosome segregation, and cytokinesis. Aurora-B is overexpressed in various cancer cells, suggesting that the kinase activity perturbs chromosomal segregation processes. Its forced overexpression induces chromosomal number instability and progressive tumorigenicity in rodent cells in vitro and in vivo. Nevertheless, based on focus formation in BALB/c 3T3 A31-1-1 cells, Aurora-B is not oncogenic. Here, we show that Aurora-B kinase activity augments Ras-mediated cell transformation. RNA interference with short hairpin RNA inhibits transformation by Ras and its upstream oncogene Src, but not by the downstream oncogene Raf. In addition, the inner centromere protein, which is a passenger protein associated with Aurora-B, has a similar ability to potentiate the activity of oncogenic Ras. These data indicate that elevated Aurora-B activity promotes transformation by oncogenic Ras by enhancing oncogenic signaling and by converting chromosome number-stable cells to aneuploid cells.

MeSH terms

  • Aneuploidy*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Aurora Kinase B
  • Aurora Kinases
  • BALB 3T3 Cells / cytology
  • BALB 3T3 Cells / drug effects
  • BALB 3T3 Cells / metabolism
  • Cell Transformation, Neoplastic / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Genes, ras / physiology*
  • Genes, src / physiology
  • Mice
  • Nocodazole / pharmacology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • raf Kinases / physiology

Substances

  • Antineoplastic Agents
  • Chromosomal Proteins, Non-Histone
  • Incenp protein, mouse
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • raf Kinases
  • Nocodazole