SUMO-2/3 Modification and Binding Regulate the Association of CENP-E with Kinetochores and Progression through Mitosis

Xiang Dong Zhang, Jacqueline Goeres, Hong Zhang, Tim J. Yen, Andrew C.G. Porter, Michael J. Matunis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)729-741
Number of pages13
JournalMolecular cell
Volume29
Issue number6
DOIs
StatePublished - Mar 28 2008

Keywords

  • CELLCYCLE
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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