Caspase-10 is an initiator caspase in death receptor signaling

A role for caspase-10, previously implicated in the autoimmune lymphoprolif erative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function independently of caspase-8 in ini tiating Fas- and tumor necrosis factor-related apoptosis-inducing ligand-re ceptor-mediated apoptosis. Moreover, Fas crosslinking in primary human T ce lls leads to the recruitment and activation of caspase-10. Fluorescent reso nance energy transfer analysis indicates that the death-effector domains of caspase-8 and -10 both interact with the death-effector domain of FADD. No netheless, we find that caspase-8 and -10 may have different apoptosis subs trates and therefore potentially distinct roles in death receptor signaling or other cellular processes.