Author: Angela Chan, MSc and Emeka Enwere, Ph.D. (see Authors page)

Revised: 23 June 2016, last major update June 2016

Copyright: (c) 2002-2016,, Inc.

PubMed Search: NFKB [title]

Cite this page: NFKB. website. Accessed June 20th, 2018.
Definition / general
  • Nuclear Factor Kappa B
  • NF-κB is a family of transcription factors that consists of five proteins: p65 (RelA), RelB, c-Rel, p105/p50 (NFKB1) and p100/p52 (NFKB2) (Oncogene 2006;25:6680)
  • These transcription factors form homodimers and heterodimers to regulate gene expression. Monomers of these transcription factors are unstable
  • NF-κB signaling is involved in a broad range of cellular functions including development, immunity, cellular differentiation, proliferation, survival and apoptosis
  • RELA: RelA, RELA proto-oncogene, p65, NFKB3
  • RELB: RelB, RELB proto-oncogene, IREL
  • c-Rel: REL, REL proto-oncogene
  • NFKB1: p50, nuclear factor kappa B subunit 1, p105, NF-κB1, NF-κB-p105
  • NFKB2: p100, nuclear factor kappa B subunit 2, p52
  • All members of the NF-κB family contain a conserved 300 amino acid N terminal "Rel homology domain" (RHD) that allows NFKB protein to bind to DNA motifs called kB elements
  • All NF-κB proteins are cytoplasmic until activated, when they translocate to the nucleus
  • Canonical NF-κB signaling involves dimers comprised of p65, RelB, c-Rel and p50. These proteins are retained in an inactive form in the cytoplasm by interaction with Inhibitor of kappa B (IκB) proteins
    • Proteasomal degradation of IκB leads to activation and nuclear translocation of canonical NF-κB dimers
  • The non-canonical NF-κB pathway does not involve IκB
    • Instead, the inactive p100 protein can be partially processed into its active p52 form
    • This dimerizes with RelB to form the transcriptionally active heterodimer
  • Canonical NF-κB signaling is induced by cytokines including TNFα, IL-6, IL-1β and Fas ligand, as well as from intracellular triggers such as genotoxic stress and ribotoxic stress induced by UV exposure
    • Non-canonical NF-κB signaling is induced by cytokines including TWEAK, RANK ligand and lymphotoxin beta
  • The non-canonical NF-κB pathway is particularly important in B cell development and maturation
Uses by pathologists
  • The complexity of NF-κB signaling makes it difficult to associate NF-κB subunit expression with particular disease states
  • NF-κB activation is prominent in inflammatory diseases such as rheumatoid arthritis, asthma, multiple sclerosis, inflammatory bowel disease and muscular dystrophies
Clinical images

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Active nuclear factor‐κB (NF‐κB)
and interleukin‐8 (IL‐8)

Microscopic (histologic) images

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Larynx SCC

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Lung adenocarcinoma

Cytology images

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Rectal cancer

Positive stains
  • Bone marrow, breast, fallopian tube, lymph node, placenta, spleen, tonsil
Negative stains
  • Brain / cerebral cortex, muscle (heart, skeletal, smooth), pancreas, prostate, testis