Caspase-8: Arbitrating Life and Death in the Innate Immune System

The canonical function of caspase-8 is to control timely cellular apoptosis to maintain tissue homeostasis and clear dysfunctional cells; however, emerging findings reveal novel, non-canonical roles of caspase in addition to regulating cellular apoptosis, including inflammatory response regulation, immune function, and cell differentiation. Furthermore, the functional versatility of caspase-8 is reported to be contingent on the presence and dimerization of various isoforms, which are produced through alternative splicing, altering its function and protein-protein interactions. Equally important are post-translational modifications, including phosphorylation and ubiquitination, which can act as a nexus to control caspase-8 activity and cellular localization. Here, we review the alternative splicing and post-translational modifications made to caspase-8 and discuss their influence on its canonical and non-canonical roles.