Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway (NF-κB pathway)

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a central coordinator of the inflammatory response, innate and adaptive immunity, and cell survival (Liu et al., 2017, Signal Transduction and Targeted Therapy). It comprises a family of five transcription factors—RelA (p65), RelB, c-Rel, p50, and p52—that form various homo- and heterodimers to regulate the expression of over 500 genes (Zhang et al., 2017, Journal of Genetics and Genomics). In resting cells, NF-κB dimers are kept inactive in the cytoplasm by Inhibitor of κB (IκB) proteins; activation occurs when the IκB kinase (IKK) complex phosphorylates IκB, marking it for proteasomal degradation and allowing NF-κB to translocate to the nucleus (Oeckinghaus & Ghosh, 2009, Cold Spring Harbor Perspectives in Biology). Aberrant NF-κB activity is strongly linked to the pathogenesis of chronic inflammatory diseases, autoimmune disorders, and various cancers, where it promotes cell proliferation and prevents apoptosis (Taniguchi & Karin, 2018, Nature Reviews Immunology). Pharmacological modulation of this pathway includes the use of proteasome inhibitors like bortezomib to prevent IκB degradation and glucocorticoids to upregulate IκB expression, though systemic inhibition remains challenging due to the pathway's essential role in normal immune function (StatPearls, 2023).

Other names

NF-kappaB signaling pathwayNFKB pathwayREL signaling pathwayNuclear factor-kappa B pathway

Inhibition of the 26S proteasome to prevent IκB degradation; inhibition of the IκB kinase (IKK) complex; glucocorticoid-mediated induction of IκBα expression; and modulation of upstream receptors such as TNFR and TLR (Liu et al., 2017; StatPearls, 2023).