Dual pathway activation by TNF. TNFR1 (as well as DR3 and DR6) recruits tissue necrosis factor–receptor associated death domain (TRADD), which mediates interactions with 2 opposing pathways. TRADD binds FADD, linking to a caspase activation pathway, and binds Rip (74-kDa protein) and tral2, which link to an NF-κB induction pathway. Targets for drug discovery are indicated. See “Extrinsic pathway” for details.