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

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling complex is a ubiquitous transcription factor system that plays a central role in regulating the expression of genes involved in immunity, inflammation, and cell survival (Source: UniProt, P19838). It typically exists as a hetero- or homodimer of proteins from the Rel family, such as p50 and p65, held in an inactive state in the cytoplasm by inhibitory IκB proteins (Source: PubMed, PMID: 11907097). Upon activation by various stimuli like cytokines or pathogens, the IκB kinase (IKK) complex phosphorylates IκB, leading to its degradation and allowing NF-κB to translocate to the nucleus to initiate gene transcription (Source: NIH, StatPearls). Dysregulation of this pathway is a hallmark of many chronic inflammatory diseases and various cancers, where it promotes tumor cell proliferation and resistance to apoptosis (Source: PubMed, PMID: 12484801). Consequently, the NF-κB complex and its upstream activators are major targets for anti-inflammatory and anti-neoplastic drug development, with agents like proteasome inhibitors and glucocorticoids modulating its activity (Source: PubChem).

Other names

NF-kappaBNFKBNuclear factor-kappa BRel family transcription factors

Drugs target the NF-κB pathway by inhibiting the IκB kinase (IKK) complex, preventing the proteasomal degradation of IκB inhibitory proteins, or blocking the nuclear translocation and DNA-binding activity of the NF-κB subunits (Source: PubMed, PMID: 15057245).