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

http://www.ncbi.nlm.nih.gov/pubmed/19822757

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 RIS Download

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

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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

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