The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis.
BACKGROUND
In eukaryotic cells, a specialized proteolysis machinery that targets proteins containing destruction-box sequences for degradation and that uses a ubiquitin ligase known as the anaphase-promoting complex/cyclosome (APC) plays a key role in the regulation of mitosis. APC-dependent proteolysis triggers the separation of sister chromatids at the metaphase-anaphase transition and the destruction of mitotic cyclins at the end of mitosis. Recently, two highly conserved WD40-repeat proteins, Cdc20 and Cdh1/Hct1, have been identified as substrate-specific regulators for APC-dependent proteolysis in the budding yeast Saccharomyces cerevisiae. Here, we have investigated the cell cycle regulation of Cdc20 and Cdh1/Hct1.


RESULTS
Whereas the levels CDH1/HCT1 RNA and Cdh1/Hct1 protein are constant throughout the cell cycle, CDC20 RNA and Cdc20 protein are present only during late S phase and mitosis and Cdc20 protein is unstable throughout the entire cell cycle. The instability of Cdc20 depends on CDC23 and CDC27, which encode components of the APC. During the G1 phase, a destruction box within Cdc20 mediates its instability, but during S phase and mitosis, although Cdc20 destruction is still dependent on CDC23 and CDC27, it does not depend on the Cdc20 destruction box.


CONCLUSIONS
There are remarkable differences in the regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself a substrate of the Cdc27 have a role in the degradation of Cdc20 during S Phase and early mitosis that is not mediated by its destruction box.
Prinz
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Hwang
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Visintin
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Amon
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A
D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; D015820:Cadherins; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000502:physiology*; D019926:Cyclin B; D016213:Cyclins / Q000235:genetics; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D008025:Ligases / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D012331:RNA, Fungal / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D015703:Antigens, CD; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C577495:CDC20 protein, S cerevisiae; C577441:CDC23 protein, S cerevisiae; C577355:CDC27 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C513384:CDH1 protein, human; C093749:CLB2 protein, S cerevisiae; D015820:Cadherins; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D016213:Cyclins; D005656:Fungal Proteins; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D002237:Carbohydrate Dehydrogenases; C019859:cellobiose-quinone oxidoreductase; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases