Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p.
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).
Huang
J N
JN
Department of Pediatric Oncology, The Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Park
I
I
Ellingson
E
E
Littlepage
L E
LE
Pellman
D
D
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
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