4. Concluding remarks

In light of the fact that the apoptotic potential of the cell is finally restricted by caspase levels and their execution efficiencies [96], the importance of check and balance for controlling caspase activity appears to be obvious. Recently, the impact of posttranslational modification on activity and stability of caspase-3 has been reviewed [97]. Apart from inhibitory and stimulatory phosphorylation, ubiquitination plays an important yet not a fully understood role. However, cIAP1-dependent ubiquitination of a processing intermediate of caspase-3 was followed by proteasome-dependent degradation of caspase-3. Interestingly, proteasome inhibitors stabilizing majorly active caspase-3 among other effector caspases enhanced apoptosis [97].

The integration of the recent knowledge on proteasomal contribution to regulation of apoptosis via UIPP and UPS might lead to a refined concept in system biology of apoptosis [98]. Despite of the remaining questions, experimental evidences indicate that tumor survival and resistance to therapeutic approaches may crucially relate to a plethora of new roles of PA28γ in the regulation of apoptosis, autophagy, inflammation, and metabolic adaptation.
