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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome / genetics
  • Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cell Line, Tumor
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Kinesin / metabolism
  • Mitosis / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction / physiology
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Sumoylation / genetics*
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitination / genetics
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • ANAPC4 protein, human
  • Apc4 Subunit, Anaphase-Promoting Complex-Cyclosome
  • RNA, Small Interfering
  • SUMO2 protein, human
  • SUMO3 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • UBA2 protein, human
  • Ubiquitins
  • KIF18B protein, human
  • Kinesin
  • SAE1 protein, human
  • Ubiquitin-Activating Enzymes