Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy

J Biomed Sci. 2005;12(2):297-310. doi: 10.1007/s11373-005-0980-0.

Abstract

Aurora kinases are emerging as key regulators of centrosome function, chromosome segregation and cytokinesis. We previously isolated Aurora-C (Aie1), a third type of Aurora kinase, in a screen for kinases expressed in mouse sperm and eggs. Currently, we know very little about the precise localization and function of Aurora-C. Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis. In order to study the potential role of Aurora-C, we examined the effects of a kinase-deficient (KD) mutant (AurC-KD) in HeLa Tet-Off cells under tetracycline control. Our results showed that overexpression of AurC-KD causes defects in cell division and induces polyploidy and apoptosis. Interestingly, AurC-KD overexpression also inhibits centromere/kinetochore localization of Aurora-B, Bub1, and BubR1, reduces histone H3 phosphorylation, and disrupts the association of INCENP with Aurora-B. Together, our results showed that Aurora-C is a chromosomal passenger protein, which may serve as a key regulator in cell division.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Cell Cycle Proteins
  • Cell Division
  • Cell Proliferation
  • Cell Separation
  • Centromere / metabolism
  • Centrosome / ultrastructure
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cytokinesis
  • DNA, Complementary / metabolism
  • Flow Cytometry
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Immunoblotting
  • In Situ Nick-End Labeling
  • Macromolecular Substances
  • Microscopy, Fluorescence
  • Mutagenesis
  • Mutation
  • Phosphorylation
  • Polyploidy
  • Protein Binding
  • Protein Kinases
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology*
  • Spindle Apparatus
  • Tetracycline / pharmacology
  • Time Factors
  • Transfection

Substances

  • Bub1b protein, mouse
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Complementary
  • Histones
  • INCENP protein, human
  • Incenp protein, mouse
  • Macromolecular Substances
  • Green Fluorescent Proteins
  • Protein Kinases
  • AURKB protein, human
  • AURKC protein, human
  • Aurkb protein, mouse
  • Aurkc protein, mouse
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • BUB1 protein, human
  • Bub1 protein, mouse
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • Tetracycline