Nuclear factor kappa B (NF-κB) (NF-κB)

Nuclear factor kappa B (NF-κB) is a pleiotropic transcription factor complex that serves as a master regulator of the inflammatory response, immune cell development, and cell survival pathways [1][2]. The NF-κB family consists of five structurally related proteins—p50, p52, RelA (p65), RelB, and c-Rel—which form various functional homo- and heterodimers that bind to specific DNA sequences to induce gene expression [3][4]. Under homeostatic conditions, NF-κB is sequestered in the cytoplasm by Inhibitor of κB (IκB) proteins; activation is typically triggered by pro-inflammatory cytokines or pathogen-associated molecular patterns that lead to the phosphorylation and subsequent proteasomal degradation of IκB, allowing NF-κB to translocate into the nucleus [2][5]. In many pathologies, particularly various cancers and chronic inflammatory diseases like rheumatoid arthritis, NF-κB is constitutively activated, promoting tumor growth, resistance to apoptosis, and sustained tissue inflammation [5][6]. Therapeutic targeting of the NF-κB pathway is a major focus in oncology and immunology, often achieved through proteasome inhibitors that prevent the release of active NF-κB or corticosteroids that increase IκB synthesis, though the broad physiological importance of the factor necessitates careful management of immunosuppressive side effects [1][6]. The term "Nuclear factor" provided is considered incomplete or generic, as it encompasses a vast category of transcription factors, though NF-κB is the most common clinically relevant reference [1].

Other names

NF-kappaBNF-kappa BNFKBNuclear factor of kappa light polypeptide gene enhancer in B-cellsRel family

Inhibition of the proteasome to prevent IκB degradation, inhibition of the IκB kinase (IKK) complex, stabilization of IκB alpha, or direct interference with DNA binding and nuclear translocation.