Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)–dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce premature mitotic exit, whereas inhibition of the APC/C-dependent degradation of cyclin B1 by MG132 induces mitotic arrest. In this study, we find that combining both drugs causes prolonged mitotic arrest in the absence of Cdk1 activity. Different Cdk1 and proteasome inhibitors produce similar results, indicating that the effect is not drug specific. We verify mitotic status by the retention of mitosis-specific markers and Cdk1 phosphorylation substrates, although cells can undergo late mitotic furrowing while still in mitosis. Overall, we conclude that continuous Cdk1 activity is not essential to maintain the mitotic state and that phosphatase activity directed at Cdk1 substrates is largely quiescent during mitosis. Furthermore, the degradation of a protein other than cyclin B1 is essential to activate a phosphatase that, in turn, enables mitotic exit.

Induction of tetraploidy through cleavage failure induces G1 arrest and senescence in primary mammalian cells but not in immortal cells. Induction of senescence occurs without DNA damage, and the capacity to become senescent appears to be a prerequisite of tetraploid arrest.

Human glioblastoma cells are motile in the absence of intact actin polymers, following suppression of actin assembly by specific inhibitors. On the other hand, suppression of microtubules completely blocks motility. These results are clearly divergent from the standard model of actin-based cell motility in mammalian cells.

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