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

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a fundamental regulator of the immune system, inflammatory responses, and cell survival (StatPearls, 2023). It comprises a family of transcription factors—RelA (p65), RelB, c-Rel, NF-κB1 (p50), and NF-κB2 (p52)—that form various homo- and heterodimers (UniProt, 2024). In its inactive state, NF-κB is sequestered in the cytoplasm by Inhibitor of kappa B (IκB) proteins; activation occurs when the IκB kinase (IKK) complex phosphorylates IκB, triggering its ubiquitination and subsequent degradation by the proteasome (NCBI, 2023). This allows NF-κB to translocate into the nucleus and induce the expression of genes involved in cytokine production, cell proliferation, and anti-apoptotic pathways. Chronic activation of NF-κB is linked to various pathologies, including inflammatory disorders like rheumatoid arthritis and multiple cancers where it promotes tumor growth and chemoresistance (PubMed, 2022). Therapeutic strategies often target the pathway via proteasome inhibitors (e.g., bortezomib) or IKK inhibitors to suppress aberrant signaling, though such interventions must balance efficacy with the risk of significant immunosuppression (Nature Reviews Drug Discovery, 2021).

Other names

NF-kappaBNFKBNuclear factor kappa BREL familyIKK/NF-kappaB pathway

Inhibition of the 26S proteasome to prevent IκB degradation; inhibition of IκB kinase (IKK) complex; stabilization of IκBα; inhibition of NF-κB nuclear translocation.