Caspase-7: a protease involved in apoptosis and inflammation

Caspase-7 was considered to be redundant with Caspase-3 because these related cysteine proteases share an optimal peptide recognition sequence and have several endogenous protein substrates in common. In addition, both caspases are proteolytically activated by the initiator Caspase-8 and -9 during death receptor- and DNA-damage-induced Apoptosis, respectively. However, a growing body of biochemical and physiological data indicate that caspase-7 also differs in significant ways from Caspase-3. For instance, several substrates are specifically cleaved by caspase-7, but not Caspase-3. Moreover, caspase-7 activation requires Caspase-1 inflammasomes under inflammatory conditions, while Caspase-3 processing proceeds independently of Caspase-1. Finally, caspase-7 deficient mice are resistant to endotoxemia, whereas Caspase-3 knockout mice are susceptible. These findings suggest that specifically interfering with caspase-7 activation may hold therapeutic value for the treatment of Cancer and inflammatory ailments.