The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20‐dependent degradation, I hypothesize that variations in Cdc20 protein levels, rather than mutations in checkpoint genes, could affect cell fate during prolonged mitotic arrest. This hypothesis is supported by experiments where manipulation of Cdc20 levels affects the response to antimitotic compounds. The observed differences (...) in Cdc20 levels between cell lines likely reflects differences in the rate of synthesis or degradation of the protein; therefore, understanding these pathways at a molecular level could pave the way for modulating the activity of Cdc20, in turn presenting novel therapeutic possibilities. (shrink)

Mitosis is a crucial phase of the cell cycle, during which several mechanisms work together to ensure accurate chromosome segregation and to eliminate defective cells if errors occur. One key mechanism is the spindle assembly checkpoint (SAC), which upon mitotic errors—such as those induced by genetic mutations, drug treatments, or environmental stresses—arrest cells in mitosis. Arrested cells may undergo apoptosis during mitosis or eventually exit mitosis even if the damage remains unrepaired. Mitotic exit is driven by a reduction in cyclin (...) B1 levels, regulated during mitosis by multiple mechanisms affecting both its synthesis and degradation. Strikingly, cells harboring the tumor suppressor p53 can monitor the duration of mitosis and encode this information as a form of “mitotic memory”. This memory influences the fate of daughter cells after mitotic exit by inducing G1 arrest through p53‐dependent expression of the cyclin‐dependent kinase (CDK) inhibitor p21. Recent studies have proposed mechanisms by which cyclin B1 levels are regulated during mitotic arrest and how p53 promotes mitotic‐arrest‐dependent transcription of p21 in G1. These findings indicate that both the expression of regulators that control mitotic duration and the activity of proteins that monitor the duration of mitosis and halt proliferation work together to determine cell fate following mitotic errors. Understanding these mechanisms offers valuable insights for cancer therapy, particularly regarding the strategic application of antimitotic agents. (shrink)