Figure 8.

The two faces of RIPK1. (A) The complex inhibitory “balancing act” between FADD–caspase-8–FLIP and RIPK3–MLKL interactions depends on RIPK1 to prevent both apoptosis and necroptosis, resulting in normal development. (B) When RIPK1 is removed, both apoptosis and necroptosis occur, and signals promote lethality. (C) Removal of either RIPK3 or MLKL in RIPK1-deficient animals (or cells) does not restore survival in RIPK1-deficient animals (or cells), as apoptosis still occurs. (D) Removal of either FADD or caspase-8 in RIPK1-deficient animals does not restore survival, as necroptosis still occurs. (E) Removal of either RIPK3 or MLKL plus either caspase-8 or FADD allows RIPK1-deficient animals to survive.