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The Doc1 subunit is a processivity factor for the anaphase-promoting complex.

Ubiquitin-mediated proteolysis of securin and mitotic cyclins is essential for exit from mitosis. The final step in ubiquitination of these and other proteins is catalysed by the anaphase-promoting complex (APC), a multi-subunit ubiquitin-protein ligase (E3). Little is known about the molecular reaction resulting in APC-dependent substrate ubiquitination or the role of individual APC subunits in the reaction. Using a well-defined in vitro system, we show that highly purified APC from Saccharomyces cerevisiae ubiquitinates a model cyclin substrate in a processive manner. Analysis of mutant APC lacking the Doc1/Apc10 subunit (APC(doc1 Delta)) indicates that Doc1 is required for processivity. The specific molecular defect in APC(doc1 Delta) is identified by a large increase in apparent K(M) for the cyclin substrate relative to the wild-type enzyme. This suggests that Doc1 stimulates processivity by limiting substrate dissociation. Addition of recombinant Doc1 to APC(doc1 Delta) fully restores enzyme function. Doc1-related domains are found in mechanistically distinct ubiquitin-ligase enzymes and may generally stimulate ubiquitination by contributing to substrate-enzyme affinity.

Pubmed ID: 12402045


  • Carroll CW
  • Morgan DO


Nature cell biology

Publication Data

November 4, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM53270
  • Agency: NIGMS NIH HHS, Id: R01 GM053270

Mesh Terms

  • Anaphase
  • Anaphase-Promoting Complex-Cyclosome
  • Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Cell Cycle
  • Cell Cycle Proteins
  • Dose-Response Relationship, Drug
  • Kinetics
  • Models, Biological
  • Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Substrate Specificity
  • Time Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases