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

Karolin Eifler (), Sabine A. G. Cuijpers, Edwin Willemstein, Jonne A. Raaijmakers, Dris El Atmioui, Huib Ovaa, René H. Medema and Alfred C. O. Vertegaal ()
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Karolin Eifler: Leiden University Medical Center
Sabine A. G. Cuijpers: Leiden University Medical Center
Edwin Willemstein: Leiden University Medical Center
Jonne A. Raaijmakers: The Netherlands Cancer Institute
Dris El Atmioui: Leiden University Medical Center
Huib Ovaa: Leiden University Medical Center
René H. Medema: The Netherlands Cancer Institute
Alfred C. O. Vertegaal: Leiden University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03486-4

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