APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit.
Cyclin degradation is central to regulation of the cell cycle. Mitotic exit was proposed to require degradation of the S phase cyclin Clb5 by the anaphase-promoting complex activated by Cdc20 (APC(Cdc20)). Furthermore, Clb5 degradation was thought to be necessary for effective dephosphorylation and activation of the APC regulatory subunit Cdh1 (also known as Hct1) and the cyclin-dependent kinase inhibitor Sic1 by the phosphatase Cdc14, allowing mitotic kinase inactivation and mitotic exit. Here we show, however, that spindle disassembly and cell division occur without significant APC(Cdc20)-mediated Clb5 degradation, as well as in the absence of both Cdh1 and Sic1. We find instead that destruction-box-dependent degradation of the mitotic cyclin Clb2 is essential for mitotic exit. APC(Cdc20) may be required for an essential early phase of Clb2 degradation, and this phase may be sufficient for most aspects of mitotic exit. Cdh1 and Sic1 may be required for further inactivation of Clb2-Cdk1, regulating cell size and the length of G1.
Wäsch
Ralph
R
The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Cross
Frederick R
FR
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D043743:Ubiquitin-Protein Ligase Complexes
C082279:CDC15 protein; C577495:CDC20 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins; D021122:Protein Subunits; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D019204:GTP-Binding Proteins; D008025:Ligases