title: Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p.
abstract: Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis is the inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APC(Cdh1) was proposed previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell cycle APC(Cdh1) is inactivated in a graded manner and is not extinguished until S phase. Complete inactivation of APC(Cdh1) requires S phase cyclins. Further, persistent APC(Cdh1) activity throughout G1 helps to ensure the proper timing of Cdc20p expression. This suggests that S phase cyclins have an important role in allowing the accumulation of mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APC(Cdh1), and APC(Cdc20).
authors.affiliation: Department of Pediatric Oncology, The Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Huang
authors.forename: I
authors.initials: I
authors.lastname: Park
authors.forename: E
authors.initials: E
authors.lastname: Ellingson
authors.forename: L E
authors.initials: LE
authors.lastname: Littlepage
authors.forename: D
authors.initials: D
authors.lastname: Pellman
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D015152:Blotting, Northern; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D019926:Cyclin B / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000378:metabolism* / Q000502:physiology*; D008025:Ligases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D004718:Saccharomycetales; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
chemical_list: C577495:CDC20 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D005656:Fungal Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases