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#Cdc20

3 public questions tagged with this topic.

Cell Cycle Regulation

What happens if APC/C-Cdc20 is inhibited?

Anaphase-promoting complex bound to coactivator Cdc20 represents irreversible executor of metaphase exit, targeting securin and cyclin B. Inhibition of this ligase through multiple mechanisms arrests cells before chromosome separation. Endogenous inhibition occurs during spindle checkpoint activation where Mitotic Checkpoint Complex binds APC/C core blocking substrate recruitment. Exogenous inhibitors apcin occupying D-box binding pocket on Cdc20 and proTAME blocking APC/C activation, or depletion of Cdc20 protein itself, mimic checkpoint. Consequence is persistence of securin which continues

Ref: Pines, Mitotic Exit Regulation by APC/C-Cdc20, Nat Rev Mol Cell Biol 2011; NCBI Bookshelf, Consequences of APC/C Inhibition.

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Cell Cycle Regulation

Which protein deactivates mitotic CDKs during mitotic exit?

Mitotic exit requires not only destruction of cyclin B but comprehensive reversal of CDK1-Cyclin B phosphorylation on hundreds of substrates. Specialized phosphatases execute this program. In budding yeast, Cdc14 is the master phosphatase. Most of the cell cycle it is sequestered in nucleolus bound to inhibitor Net1 or Cfi1. Two release pathways operate sequentially: the Cdc Fourteen Early Anaphase Release pathway involving separase, Slk19, Spo12 and Zds1/Zds2 provides transient liberation in early anaphase, while the Mitotic Exit Network composed of Tem1, Cdc15 and Dbf2-Mob1 kinases sustains

Ref: Stegmeier & Amon, Closing Mitosis: Role of Cdc14 Phosphatases, Annu Rev Genet 2004; Alberts et al., Chapter 17, Mitotic Exit Control.

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Cell Cycle Regulation

What happens if Cdc20 is inhibited?

Anaphase entry requires anaphase-promoting complex/cyclosome (APC/C) activated by co-activator Cdc20, which targets securin and cyclin B for proteasomal degradation via K11-linked polyubiquitination. Securin normally binds and inhibits separase, protease that cleaves cohesin subunit Rad21 holding sister chromatids together. When APC/C-Cdc20 destroys securin, liberated separase removes cohesin, allowing sister chromatids to separate toward opposite poles. If Cdc20 is absent, inhibited by MCC, or chemically blocked, APC/C remains inactive, securin and cyclin B persist, separase stays inhibited,

Ref: Peters, Nature Rev Mol Cell Biol 2006, APC/C and Cdc20; Sivakumar & Gorbsky, Nature Rev Mol Cell Biol 2015, Spindle Checkpoint.

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