SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis

Mol Cell. 2008 Mar 28;29(6):729-41. doi: 10.1016/j.molcel.2008.01.013.


SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology*
  • Centromere / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cysteine Endopeptidases / metabolism
  • DNA Topoisomerases / metabolism
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Kinetics
  • Kinetochores / metabolism*
  • Metaphase
  • Mitosis / physiology*
  • Protein Binding
  • SUMO-1 Protein / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Ubiquitins / metabolism*


  • Chromosomal Proteins, Non-Histone
  • SUMO-1 Protein
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Ubiquitins
  • centromere protein E
  • Cysteine Endopeptidases
  • SENP2 protein, human
  • DNA Topoisomerases