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

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a master regulator of the inflammatory response and cellular survival. It comprises a family of inducible transcription factors, including p50, p52, RelA (p65), RelB, and c-Rel, which regulate the expression of genes involved in innate and adaptive immunity, cell proliferation, and apoptosis [1, 2]. In most resting cells, NF-κB dimers are sequestered in the cytoplasm by inhibitors of κB (IκB) proteins; activation occurs when the IκB kinase (IKK) complex phosphorylates IκB, triggering its proteasomal degradation and allowing NF-κB to translocate to the nucleus [3, 5]. Chronic activation of this pathway is linked to various pathologies, including rheumatoid arthritis, inflammatory bowel disease, and multiple cancers, where it promotes tumor cell survival and treatment resistance [5, 6]. Therapeutic strategies include proteasome inhibitors like bortezomib, which prevent IκB degradation, and various IKK inhibitors currently under investigation [3, 4]. However, because NF-κB is essential for normal immune function, systemic inhibition poses significant safety concerns, including severe immunosuppression and increased susceptibility to infections [6].

Other names

NF-kappaB signaling pathwayNFKB pathwayNuclear factor-kappa B signalingNF-kappa-B and downstream mediators

Inhibition of the IκB kinase (IKK) complex, inhibition of the 26S proteasome to prevent IκB degradation, interference with NF-κB nuclear translocation, and inhibition of NF-κB DNA binding activity.