SUMOylation modulates the function of Aurora-B kinase

J Cell Sci. 2010 Aug 15;123(Pt 16):2823-33. doi: 10.1242/jcs.065565. Epub 2010 Jul 27.

Abstract

Aurora kinases are central regulators of mitotic-spindle assembly, chromosome segregation and cytokinesis. Aurora B is a member of the chromosomal passenger complex (CPC) with crucial functions in regulation of the attachment of kinetochores to microtubules and in cytokinesis. We report here that Aurora B contains a conserved SUMO modification motif within its kinase domain. Aurora B can bind SUMO peptides in vitro when bound to the IN-box domain of its CPC partner INCENP. Mutation of Lys207 to arginine (Aurora B(K207R)) impairs the formation of conjugates of Aurora B and SUMO in vivo. Expression of the SUMO-null form of Aurora B results in abnormal chromosome segregation and cytokinesis failure and it is not able to rescue mitotic defects in Aurora-B-knockout cells. These defects are accompanied by increased levels of the CPC on chromosome arms and defective centromeric function, as detected by decreased phosphorylation of the Aurora-B substrate CENP-A. The Aurora-B(K207R) mutant does not display reduced kinase activity, suggesting that functional defects are probably a consequence of the altered localization, rather than decreased intrinsic kinase activity. These data suggest that SUMOylation of Aurora B modulates its function, possibly by mediating the extraction of CPC complexes from chromosome arms during prometaphase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / metabolism
  • Cell Survival
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation
  • Cytokinesis / genetics
  • HeLa Cells
  • Humans
  • Mice
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • SUMO-1 Protein / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Sumoylation
  • Transfection

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • SUMO-1 Protein
  • AURKB protein, human
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases