Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B

J Biol Chem. 2015 Jul 10;290(28):17546-58. doi: 10.1074/jbc.M115.652453. Epub 2015 May 18.

Abstract

Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation.

Keywords: Aurora kinase; INCENP; TPX2; cell cycle; checkpoint control; mitotic spindle; protein kinase; protein phosphorylation; spindle assembly..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase A / chemistry
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism*
  • Aurora Kinase B / chemistry
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism*
  • Cell Compartmentation
  • Cell Cycle Checkpoints
  • Centrosome / metabolism
  • Chromatin / metabolism
  • Evolution, Molecular
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Kinetochores / metabolism
  • Mitosis
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Spindle Apparatus / metabolism

Substances

  • Chromatin
  • Histones
  • Recombinant Fusion Proteins
  • AURKA protein, human
  • AURKB protein, human
  • Aurora Kinase A
  • Aurora Kinase B