TNF-alpha Signalling Pathway

The Tumor Necrosis Factor alpha is a proinflammatory cytokine belonging to the TNF superfamily. It signals through 2 separate receptors - TNFRSF1A and TNFRSF1B, both members of the TNF receptor superfamily. Activation by the homotrimeric ligand results in receptor trimerization. TNFRSF1A trimers result in the activation of NF-kB through MAPK and caspase pathways leading to apoptosis, whereas a heterocomplex of both TNFRSF1A and TNFRSF1B recruits proteins such as BIRC2 and BIRC3, which are apoptotic inhibitors. As both TNF alpha and IL-1 stimulate the MAPK signaling module and activate NFkB, they are synergistic and complement each other's activity.