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UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex.

The Anaphase-Promoting Complex (APC) is an E3 ubiquitin ligase that regulates mitosis and G1 by sequentially targeting cell-cycle regulators for ubiquitination and proteasomal degradation. The mechanism of ubiquitin chain formation by APC and the resultant chain topology remains controversial. By using a single-lysine APC substrate to dissect the topology of ubiquitinated substrates, we find that APC-catalyzed ubiquitination has an intrinsic preference for the K11 linkage of ubiquitin that is essential for substrate degradation. K11 specificity is determined by an E2 enzyme, UBE2S/E2-EPF, that elongates ubiquitin chains after the substrates are pre-ubiquitinated by UbcH10 or UbcH5. UBE2S copurifies with APC; dominant-negative Ube2S slows down APC substrate degradation in functional cell-cycle extracts. We propose that Ube2S is a critical, unique component of the APC ubiquitination pathway.

Pubmed ID: 20080579


  • Wu T
  • Merbl Y
  • Huo Y
  • Gallop JL
  • Tzur A
  • Kirschner MW


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

Publication Data

January 26, 2010

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 5R01GM39023-21

Mesh Terms

  • Anaphase-Promoting Complex-Cyclosome
  • Biocatalysis
  • Cell Cycle
  • HeLa Cells
  • Humans
  • Lysine
  • Mutation
  • Neoplasm Proteins
  • Protein Binding
  • Securin
  • Substrate Specificity
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes