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Identification of a physiological E2 module for the human anaphase-promoting complex.

Ubiquitination by the anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The human APC/C promotes the degradation of mitotic regulators by assembling K11-linked ubiquitin chains, the formation of which is initiated by its E2 UbcH10. Here, we identify the conserved Ube2S as a K11-specific chain elongating E2 for human and Drosophila APC/C. Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity. While depletion of Ube2S already inhibits APC/C in cells, the loss of the complete UbcH10/Ube2S-module leads to dramatic stabilization of APC/C substrates, severe spindle defects, and a strong mitotic delay. Ube2S and UbcH10 are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.

Pubmed ID: 19822757

Authors

  • Williamson A
  • Wickliffe KE
  • Mellone BG
  • Song L
  • Karpen GH
  • Rape M

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 27, 2009

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM066272
  • Agency: NIGMS NIH HHS, Id: R01 GM066272
  • Agency: NIGMS NIH HHS, Id: R01 GM066272-07
  • Agency: NIGMS NIH HHS, Id: R01 GM083064

Mesh Terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Biocatalysis
  • Drosophila melanogaster
  • HeLa Cells
  • Humans
  • Mitosis
  • Protein Binding
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes