title: Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism.
abstract: BACKGROUND
  Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the anaphase-promoting complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood.
  
  
  RESULTS
  Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20's C box. Cdc20 turnover by this intramolecular mechanism is cell cycle regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination.
  
  
  CONCLUSIONS
  We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Foe
authors.forename: Scott A
authors.initials: SA
authors.lastname: Foster
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Cheung
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: DeLuca
authors.forename: David O
authors.initials: DO
authors.lastname: Morgan
authors.forename: David P
authors.initials: DP
authors.lastname: Toczyski
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D001120:Arginine / Q000378:metabolism; D015153:Blotting, Western; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006207:Half-Life; D007532:Isoleucine / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C577495:CDC20 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D007532:Isoleucine; D001120:Arginine; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome
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