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

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) – DNA transcriptional complex is a master regulator of the mammalian immune system and inflammatory response. It consists of a family of inducible transcription factors, including p50, p52, p65 (RelA), c-Rel, and RelB, which form various homo- and heterodimers that bind to specific DNA sequences known as κB sites (Oeckinghaus & Ghosh, 2009). In resting cells, NF-κB dimers are sequestered in the cytoplasm by inhibitory IκB proteins; however, upon activation by stimuli such as cytokines (TNF-α, IL-1), pathogen-associated molecular patterns, or cellular stress, IκB is phosphorylated by the IKK complex and degraded by the proteasome (Hayden & Ghosh, 2008). This allows the NF-κB dimer to translocate into the nucleus and bind to DNA, forming the transcriptional complex that initiates the expression of genes involved in cell survival, proliferation, and the pro-inflammatory response. Dysregulation of this complex is a hallmark of many human diseases, particularly chronic inflammatory disorders and various cancers, where it promotes tumor cell resistance to apoptosis and supports the tumor microenvironment (Karin, 2006). Because of its central role in disease pathogenesis, the NF-κB–DNA complex and its upstream regulatory pathway are major targets for therapeutic intervention, with drugs such as proteasome inhibitors and corticosteroids being widely used to modulate its activity (Baud & Karin, 2009).

Other names

NF-kappaB-DNA complexNF-kB-DNA complexNuclear factor kappa B-DNA complexNF-kappa-B-DNA complexNF-κB transcriptional complex

Inhibition of the NF-κB signaling pathway through proteasome inhibition (preventing IκB degradation), IKK complex inhibition, induction of IκB expression, or direct interference with NF-κB DNA-binding activity.