Figure 1.

Cell cycle–dependent regulation of Mcl-1 levels and mitotic cell death.

The levels of the anti-apoptotic protein Mcl-1 (MCL1) vary during the cell cycle, reaching a peak around G2 and declining during mitosis due to ubiquitin proteasome-mediated degradation initiated by the APC/C (anaphase-promoting complex or cyclosome). The activity of the APC/C towards Mcl-1 is not affected by the spindle assembly checkpoint, which holds cells in a prometaphase-like state until proper chromosome attachment to spindle microtubules has been completed. Mcl-1 levels drop below a critical level during a prolonged mitotic arrest caused by unresolved spindle assembly, for instance due to disruption of microtubules by a drug, resulting in mitotic cell death by the intrinsic apoptotic pathway.