Caspase 8 is at the top of the hierarchy of the caspase cascade and is considered an initiator caspase. It exists in the cell as an inactive 55?kDa proenzyme. It is converted to the active form, consisting of 18?kDa and 11?kDa subunits, upon its recruitment to the cytoplasmic domain of activated death receptors such as CD95 or TNFR via the adapter protein FADD. The activation of the proenzyme is triggered by the protein′s aggregation, which leads to auto- or transprocessing. Caspase?8 activates downstream caspases (caspases?3, 6, and 7) that cleave key cellular substrates and lead to apoptotic death of the cells.
