title: Cdc20 protein contains a destruction-box but, unlike Clb2, its proteolysisis not acutely dependent on the activity of anaphase-promoting complex.
abstract: Both chromosome segregation and the final exit from mitosis require a ubiquitin-protein ligase called anaphase-promoting complex (APC) or cyclosome. This multiprotein complex ubiquitinates various substrates, such as the anaphase inhibitor Pds1 and mitotic cyclins, and thus targets them for proteolysis by the 26S proteasome. The ubiquitination by APC is dependent on the presence of a destruction-box sequence in the N-terminus of target proteins. Recent reports have strongly suggested that Cdc20, a WD40 repeat-containing protein required for nuclear division in the budding yeast Saccharomyces cerevisiae, is essential for the APC-mediated proteolysis. To understand the function of CDC20, we have studied its regulation in some detail. The expression of the CDC20 gene is cell-cycle regulated such that it is transcribed only during late S phase and mitosis. Although the protein is unstable to some extent through out the cell cycle, its degradation is particularly enhanced in G1. Cdc20 contains a destruction box sequence which, when mutated or deleted, stabilizes it considerably in G1. Surprisingly, we find that while the inactivation of APC subunits Cdc16, Cdc23 or Cdc27 results in stabilization of the mitotic cyclin Clb2 in G1, the proteolytic destruction of Cdc20 remains largely unaffected. This suggests the existence of proteolytic mechanisms in G1 that can degrade destruction-box containing proteins, such as Cdc20, in an APC-independent manner.
authors.affiliation: Institute of Molecular Biology, Singapore.
authors.forename: P Y
authors.initials: PY
authors.lastname: Goh
authors.forename: H H
authors.initials: HH
authors.lastname: Lim
authors.forename: U
authors.initials: U
authors.lastname: Surana
mesh_terms: D020816:Amino Acid Motifs; D000705:Anaphase / Q000502:physiology*; D064173:Anaphase-Promoting Complex-Cyclosome; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C577397:CDC16 protein, S cerevisiae; C577495:CDC20 protein, S cerevisiae; C577441:CDC23 protein, S cerevisiae; C577355:CDC27 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D017489:CDC28 Protein Kinase, S cerevisiae; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex