Mitotic Kinase Aurora-B Is Regulated by SUMO-2/3 conjugation/deconjugation During Mitosis

Genes Cells. 2011 Jun;16(6):652-69. doi: 10.1111/j.1365-2443.2011.01521.x. Epub 2011 May 10.

Abstract

The small ubiquitin-related modifier (SUMO) system of higher eukaryotes plays important roles in normal cell division, especially in chromosome segregation. However, only a few mitotic SUMO substrates have been identified in mammals. Here, we show that the mitotic kinase Aurora-B can be modified by SUMO. The E3 SUMO-protein ligase PIAS3 [protein inhibitor of activated STAT (signal transducer and activator of transcription)] dramatically enhanced poly-SUMO-2/3 conjugation of Aurora-B, whereas the SUMO-specific isopeptidase SENP2 (Sentrin/SUMO-specific protease) specifically deconjugated SUMO from Aurora-B. The Lys-202 residue on human Aurora-B was preferentially modified by SUMO, and enhancement of SUMOylation in cells facilitated Aurora-B autophosphorylation, which is essential for its activation. Conversely, SENP2-mediated deSUMOylation of Aurora-B down-regulated its autophosphorylation in cells and also impaired its re-activation in Aurora inhibitor VX-680-treated mitotic cells. Poly-SUMO-2 conjugation of Aurora-B occurred during the M phase of the cell cycle, and both SUMO-2 and PIAS3 were localized adjacent to Aurora-B in the kinetochores in early mitosis. Based on these results, we propose that Aurora-B is a novel mitotic SUMO substrate and that its kinase activity is fine-tuned by the SUMO system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Binding Sites / physiology
  • Cysteine Endopeptidases / metabolism
  • Enzyme Activation / physiology
  • G1 Phase / physiology
  • Gene Expression Regulation, Enzymologic*
  • HeLa Cells
  • Humans
  • Mitosis / physiology*
  • Molecular Chaperones / metabolism
  • Phosphorylation / physiology
  • Protein Binding
  • Protein Inhibitors of Activated STAT / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation / physiology

Substances

  • Molecular Chaperones
  • PIAS3 protein, human
  • Protein Inhibitors of Activated STAT
  • Small Ubiquitin-Related Modifier Proteins
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Cysteine Endopeptidases
  • SENP2 protein, human