TNF-dependent hyperactivation of RIPK1-dependent cytotoxic signaling during embryogenesis and inflammation.

In this issue of PLOS Biology, Zhang and colleagues unveil a complex midgestational death during embryogenesis of mice harboring caspase-8 cleavage-resistant receptor-interacting protein (RIP) kinase (RIPK)1. Tumor necrosis factor (TNF) receptor (TNFR)1-dependent signaling drives cell death through a novel pathway requiring synergism between apoptotic and pyroptotic caspases.