Caspase-8: Arbitrating Life and Death in the Innate Immune System
Sahil Gupta, M. López, Amin M. Ektesabi, James N. Tsoporis, Chirag M. Vaswani, Shil Y. Gandhi, Gregory D. Fairn, Claúdia C. dos Santos, John C. Marshall
Abstract
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.