A model for Mcl-1 regulation in apoptosis promoted by proteasome inhibitors. Proteasome inhibitors activate the intrinsic apoptotic pathway by releasing mitochondrial proapoptotic factors. This results in activation of the caspase cascade and apoptosis progression. However, proteasome inhibition impedes Mcl-1 down-regulation, an event that is normally observed during apoptosis and which contributes to speeding up cell demise. This molecular side effect of proteasome inhibitors slows down their cytotoxic activity.