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Nat Commun. 2018 Mar 16;9(1):1119. doi: 10.1038/s41467-018-03486-4.

SUMO targets the APC/C to regulate transition from metaphase to anaphase.

Author information

1
Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands. k.eifler-olivi@imb-mainz.de.
2
Institute of Molecular Biology gGmbH, Ackermannweg 4, Mainz, 55128, Germany. k.eifler-olivi@imb-mainz.de.
3
Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
4
Oncode Institute and Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
5
Oncode Institute and Department of Chemical Immunology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
6
Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands. vertegaal@lumc.nl.

Abstract

Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation is crucial for accurate progression of cells through mitosis and increases APC/C ubiquitylation activity toward a subset of its targets, including the newly identified target KIF18B. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal how SUMO and ubiquitin cooperate to drive mitosis.

PMID:
29549242
PMCID:
PMC5856775
DOI:
10.1038/s41467-018-03486-4
[Indexed for MEDLINE]
Free PMC Article

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