TNF receptor 1 signalling. TNF receptor 1 (TNFR1) ligation induces death domain-mediated recruitment of TNFR1/TRADD/TRAF2/RIP1 (complex I) at the cell surface, and this complex initiates NF-κB activation, which in turn drives production of cFLIP, an apoptotic inhibitor. Activated TNFR1 is then endocytosed and the TRADD/TRAF2/RIP1 complex dissociates from the receptor in a temporal manner. This complex then recruits FADD and caspase-8 (complex II), which activates the apoptotic machinery, provided that the levels of cFLIP are low enough to remove inhibition. Adapted from . In a second model, proposed by Schneider-Brachart and colleagues , the apoptotic complex is internalised upon assembly in receptosomes, which fuse with golgi vesicles and signal for apoptosis from within the cell. NO, nitric oxide; ROS, reactive oxygen species.