High impact information on CDC20

• Kinetochores that have not yet attached to microtubules catalyze the sequestration of Cdc20 by an inhibitor called Mad2 [1].
• Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex [2].
• Hct1 and the related Cdc20 may function as substrate-specific regulators of proteolysis during mitosis [3].
• Mitotic exit was proposed to require degradation of the S phase cyclin Clb5 by the anaphase-promoting complex activated by Cdc20 (APC(Cdc20)) [4].
• Mad2 and Mad3 coprecipitated with Cdc20 at all stages of the cell cycle [5].

Biological context of CDC20

• Overexpression of either CDC20 or CDH1 was sufficient to induce APC-dependent proteolysis of the appropriate target in stages of the cell cycle in which substrates are normally stable [6].
• In Saccharomyces cerevisiae, chromosome segregation also requires the CDC20 gene, whose product contains WD40 repeats [11,12] [7].
• CDC20 overexpression was unable to promote anaphase in cells deficient in APC function [8].
• Therefore, we suggest that the DNA damage-induced checkpoint controls prevent mitosis by inhibiting the nuclear division pathway requiring CDC20 function [9].
• Cdc20, an activator of the anaphase-promoting complex (APC), is also required for the exit from mitosis in Saccharomyces cerevisiae [10].

Anatomical context of CDC20

• We find that upon spindle checkpoint activation by microtubule inhibitors benomyl or nocodazole, wild-type Saccharomyces cerevisiae contains less Cdc20p than spindle checkpoint mutants do, whereas their CDC20 mRNA levels are similar [11].
• Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells [12].
• In HeLa cells, Cdc20 is associated with the kinase aurora2/Aik [13].
• Cortex, a Drosophila gene required to complete oocyte meiosis, is a member of the Cdc20/fizzy protein family [14].

Associations of CDC20 with chemical compounds

• Here we find that the cyclic-AMP-dependent protein kinase (PKA) pathway supports Chk1 in the regulation of mitosis by targeting the mitotic inducer Cdc20 [15].

Physical interactions of CDC20

• The checkpoint proteins Mad2 and Mad3/BubR1 bind to Cdc20, although how they inhibit APC(Cdc20) is unclear [16].
• Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae [17].
• Finally, this bacterially expressed Hsl1p fusion protein interacted with Cdc20p and Cdh1p either translated in vitro or expressed in and purified from insect cells [18].
• Here we find that Pds1 interacts directly with Cdc20 and that this interaction requires Pds1's destruction box [19].

Regulatory relationships of CDC20

• Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex [20].
• Overproduction of Cdc20 does not influence the arrest phenotype of the cdc mutants whose cell cycle block is independent of RAD9-mediated checkpoint control [9].
• Cdc20p may promote the APC-dependent proteolytic degradation of Pds1p and other factors that act to inhibit cell cycle progression through mitosis [8].
• Although the precise mechanism of APC inhibition by Cla4t remains to be elucidated, our results suggest that Cla4 and Ste20 may regulate the first wave of cyclinB proteolysis mediated by Cdc20/APC, which has been shown to be crucial for activation of the mitotic exit network (MEN) [21].
• The WD repeat protein Cdc20 is essential for progression through mitosis because it is required to activate ubiquitin ligation by the anaphase-promoting complex (APC/C) [22].

Other interactions of CDC20

• CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis [6].
• These findings implicate Mad3p as a pseudosubstrate inhibitor of APC(Cdc20), competing with APC substrates for Cdc20p binding [16].
• Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct 1 and Cdc20 [23].
• 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 [24].
• The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis [24].

Analytical, diagnostic and therapeutic context of CDC20

• Consistent with this interpretation, we find that cdc20 cells arrested by alpha-factor or at the restrictive temperature accumulate anomalous microtubule structures, as detected by indirect immunofluorescence [25].
• Mutagenesis and NMR titration experiments show that a C-terminal flexible region of Mad2 is required for binding to Cdc20 [26].
• Using deletion mutagenesis and peptide mapping, we have identified the sequences in Cdc20 that target it to Mad2 and the APC, respectively [27].

References