Securin and B-cyclin/CDK are the only essential targets of the APC.
The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis. The complex is composed of at least thirteen core subunits, eight of which are essential, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential). Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.
Thornton
Brian R
BR
Cancer Research Institute, S-332 Department of Biochemistry and Biophysics University of California, San Francisco 2340 Sutter Street, San Francisco, CA 94115, USA.
Toczyski
David P
DP
D064173:Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; D021122:Protein Subunits; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D018844:Cyclin-Dependent Kinases