Caspase-10 is an initiator caspase in death receptor signaling

A role for Caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that Caspase-10 can function independently of Caspase-8 in initiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-receptor-mediated Apoptosis. Moreover, Fas crosslinking in primary human T cells leads to the recruitment and activation of Caspase-10. Fluorescent resonance energy transfer analysis indicates that the death-effector domains of Caspase-8 and -10 both interact with the death-effector domain of FADD. Nonetheless, we find that Caspase-8 and -10 may have different Apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes.