Cdc20, an Activator at Last

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94115, USA.
Molecular cell (Impact Factor: 14.02). 12/2008; 32(4):460-1. DOI: 10.1016/j.molcel.2008.11.006
Source: PubMed


Cdc20 was first identified as an essential gene required for the metaphase-to-anaphase transition in yeast. Subsequent work suggested that the Drosophila Cdc20 homolog, Fizzy, was required for the turnover of mitotic cyclins (reviewed in Thornton and Toczyski, 2006). It soon became apparent that Fizzy/Cdc20 and a similar protein, Fizzy-related/Cdh1, promoted anaphase-promoting complex (APC) function, although the mechanism by which it did this was not clear. What was clear early on, however, was that the regulation of APC activity on its substrates relied largely on the regulation of Cdc20 and Cdh1. Thus, not only were these molecules required for APC function, they were also the targets of its regulation, either by their degradation, their phosphorylation, or the binding of protein inhibitors. Now, Kimata et al. (2008) have exploited an unusual APC substrate, Nek2A, which they had previously shown interacts directly with the core APC independently of Cdc20, to identify a previously unappreciated role for Cdc20 in direct APC activation.

5 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The execution of meiotic divisions in Saccharomyces cerevisiae is regulated by anaphase-promoting complex/cyclosome (APC/C)-mediated protein degradation. During meiosis, the APC/C is activated by association with Cdc20p or the meiosis-specific activator Ama1p. We present evidence that, as cells exit from meiosis II, APC/C(Ama1) mediates Cdc20p destruction. APC/C(Ama1) recognizes two degrons on Cdc20p, the destruction box and destruction degron, with either domain being sufficient to mediate Cdc20p destruction. Cdc20p does not need to associate with the APC/C to bind Ama1p or be destroyed. Coimmunoprecipitation analyses showed that the diverged amino-terminal region of Ama1p recognizes both Cdc20p and Clb1p, a previously identified substrate of APC/C(Ama1). Domain swap experiments revealed that the C-terminal WD region of Cdh1p, when fused to the N-terminal region of Ama1p, could direct most of Ama1p functions, although at a reduced level. In addition, this fusion protein cannot complement the spore wall defect in ama1Δ strains, indicating that substrate specificity is also derived from the WD repeat domain. These findings provide a mechanism to temporally down-regulate APC/C(Cdc20) activity as the cells complete meiosis II and form spores.
    Molecular biology of the cell 02/2011; 22(3):315-26. DOI:10.1091/mbc.E10-04-0360 · 4.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The spindle assembly checkpoint (SAC) ensures accurate segregation of chromosomes by monitoring kinetochore attachment of spindles during mitosis. Proper progression of mitosis depends on orderly ubiquitination and subsequent degradation of various mitotic inhibitors. At the molecular level, upon removal of SAC, Cdc20 activates E3 ubiquitin ligase anaphase-promoting complex/cyclosome that, along with E2 ubiquitin-conjugating enzyme UbcH10, executes this function. Both Cdc20 and UbcH10 are overexpressed in many cancer types and are associated with defective SAC function leading to chromosomal instability. The precise mechanism of correlated overexpression of these two proteins remains elusive. We show that Cdc20 transcriptionally up-regulates UbcH10 expression. The WD40 domain of Cdc20 is required for this activity. Physical interaction between Cdc20 and anaphase-promoting complex/cyclosome-CBP/p300 complex and its subsequent recruitment to the UBCH10 promoter are involved in this transactivation process. This transcriptional regulatory function of Cdc20 was observed to be cell cycle-specific. We hypothesize that this co-regulated overexpression of both proteins contributes to chromosomal instability.
    Journal of Biological Chemistry 03/2011; 286(18):15666-77. DOI:10.1074/jbc.M110.160671 · 4.57 Impact Factor
  • W.L. Yang · J Li · P An · A.M. Lei ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The cell division cycle protein 20 (CDC20) is an essential regulator of cell division, encoded by the CDC20 gene. However, the role of CDC20 in bovine oocyte maturation is unknown. In this study, CDC20 morpholino antisense oligonucleotides (MOs) were microinjected into the cytoplasm of bovine oocytes to block the translation of CDC20 mRNA. CDC20 downregulation significantly reduced the rate of first polar body emission (PB1). Further analysis indicated that oocytes treated with CDC20 MO arrested before or at meiotic stage I with abnormal spindles. To further confirm the functions of CDC20 during oocyte meiotic division, CDC20 MOs were microinjected into oocytes together with a supplementary PB1. The results showed that newly synthesized CDC20 was not necessary at the meiosis II-to-anaphase II transition. Our data suggest that CDC20 is required for spindle assembly, chromosomal segregation, and PB1 extrusion during bovine oocyte maturation.
    Theriogenology 11/2013; 81(4). DOI:10.1016/j.theriogenology.2013.11.005 · 1.80 Impact Factor

Similar Publications


5 Reads
Available from