Tumor necrosis factor and nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway (TNF–NF-κB signaling pathway)

The TNF–NF-κB signaling pathway is a crucial mediator of inflammation and immune responses, linking extracellular signals provided by the cytokine tumor necrosis factor alpha (TNF-α) to changes in gene expression mediated by the NF-κB family of transcription factors. After TNF binds to its cell surface receptors (TNFR1 or TNFR2), adaptor proteins (such as TRADD and TRAF2) are recruited, leading to the activation of the IκB kinase (IKK) complex. IKK then phosphorylates inhibitors of NF-κB (IκBs), causing their degradation and allowing NF-κB dimers to translocate to the nucleus where they induce gene expression governing inflammation, cell survival, and immune responses. Dysregulation of this pathway is implicated in numerous diseases, including chronic inflammatory and autoimmune disorders, cancer, and neurodegenerative conditions. Many biologic therapies, such as anti-TNF antibodies, target components of this pathway for the treatment of autoimmune diseases like rheumatoid arthritis and Crohn’s disease[2][1][6][4][5].

Other names

TNF-alpha/NF-kappaB pathwayTNF/NF-κB pathwayTNF signaling pathwayNF-κB pathwayTumor necrosis factor signaling pathway

TNF inhibition (by monoclonal antibodies or decoy receptors, preventing TNF from binding its receptors and thus blocking downstream NF-κB activation) Inhibition of NF-κB activation (in experimental approaches, through blockade of IκB kinase, etc.)