TNF family members play important roles in various physiological and pathological processes, including cell proliferation, differentiation, apoptosis, modulation of immune responses, and induction of inflammation. Members of the TNFR superfamily can send ...both survival and death signals to cells. TNF-Alpha (Tumor Necrosis Factor-Alpha), a potent cytokine, elicits a broad spectrum of biologic responses, which are mediated by binding to a cell surface receptor. TNF has been considered as an anti-cancer agent. TNF acts through two receptors, TNFR1 and TNFR2. TNFR1 is expressed by all human tissues and is the major signaling receptor for TNF-Alpha. TNFR2 is mostly expressed in immune cells and mediates limited biological responses. TNFR1 contains a cytoplasmic DD (Death Domain) required for signaling pathways associated with apoptosis and NF-KappaB (Nuclear Factor-KappaB) activation. TNF-induced receptor trimerization aggregates the DD of TNFR1 and recruits the adapter protein TRADD (TNFR-Associated Death Domain). This in turn promotes the recruitment of the DD-containing cytoplasmic proteins FADD (Fas Associated Death Domain),MADD (MAPK Activating Death Domain),RAIDD (RIP-Associated ICH-1/CED-3-homologous protein with a Death Domain) TRAF1/2 (TNF Receptor Associated Factor-1/2) and RIP (Receptor Interacting Protein) to form an active TNFR1 signaling complex containing CIAP (cellular Inhibitor of Apoptosis).
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