Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.
Activation of the anaphase-promoting complex (APC) is required for anaphase initiation and for exit from mitosis. We show that APC is activated during mitosis and G1 by two regulatory factors, hCDC20 and hCDH1. These proteins directly bind to APC and activate its cyclin ubiquitination activity. hCDC20 confers a strict destruction-box (D-box) dependence on APC, while hCDH1 shows a much more relaxed specificity for the D-box. In HeLa cells, the protein levels of hCDC20 as well as its binding to APC peak in mitosis and decrease drastically at early G1. Thus, hCDC20 is the mitotic activator of APC and directs the degradation of substrates containing the D-box. The hCDH1 protein level remains constant during the cell cycle and may target specific substrates lacking the D-box in G1, such as polo-like kinase, for ubiquitination.
Fang
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Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yu
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Kirschner
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MW
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008025:Ligases / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D010063:Ovum / Q000378:metabolism; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D014981:Xenopus
C577495:CDC20 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases