CDC20

The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the CDC20 gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/C), a large 11-13 subunit complex that initiates chromatid separation and entrance into anaphase. The APC/CCdc20 protein complex has two main downstream targets. Firstly, it targets securin for destruction, enabling the eventual destruction of cohesin and thus sister chromatid separation. It also targets S and M-phase (S/M) cyclins for destruction, which inactivates S/M cyclin-dependent kinases (Cdks) and allows the cell to exit from mitosis. A closely related protein, Cdc20homologue-1 (Cdh1) plays a complementary role in the cell cycle. CDC20 appears to act as a regulatory protein interacting with many other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes: nuclear movement prior to anaphase, and chromosome separation. CDC20, along with a handful of other Cdc proteins, was discovered in the early 1970s when Hartwell and colleagues made cell-division cycle mutants that failed to complete major events in the cell cycle in the yeast strain S. cerevisiae. Hartwell found mutants that did not enter anaphase and thus could not complete mitosis; this phenotype could be traced back to the CDC20 gene. However, even after the biochemistry of the protein was eventually elucidated, the molecular role of CDC20 remained elusive until the discovery of the APC/C in 1995. CDC20 is a protein related to the beta subunit of heterotrimeric G proteins. Near its C-terminus it contains seven WD40 repeats, which are multiple short, structural motifs of around 40 amino acids that often play a role in binding with larger protein complexes. In the case of CDC20, they arrange into a seven-bladed beta propeller. The human CDC20 is about 499 amino acids long, and contains at least four phosphorylation sites near the N-terminus.