Inhibitory kappa B kinase beta–Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway (IKKβ–NF-κB signaling pathway)

The IKKβ–NF-κB signaling pathway is a central intracellular signaling cascade regulating immune, inflammatory, and survival responses. Activation typically begins with extracellular signals (e.g., cytokines, microbial components) stimulating receptors such as TNFRs or Toll-like receptors, which, via adaptor proteins (e.g., TRAF6), recruit the IKK complex. The IKK complex, composed of IKKβ (the main kinase for the canonical pathway), IKKα, and regulatory NEMO/IKKγ, phosphorylates inhibitory IκB proteins. This triggers ubiquitination and degradation of IκB, liberating NF-κB to translocate into the nucleus and activate transcription of genes involved in inflammation, immune response, cell survival, and proliferation. Dysregulation of the pathway is implicated in multiple diseases, making its components attractive drug targets.

Other names

Canonical NF-κB pathwayClassical NF-κB pathwayIKKβ-dependent NF-κB pathway

Inhibition of IKKβ blocks phosphorylation of IκB, retaining NF-κB in the cytoplasm, thus preventing transcription of pro-inflammatory and proliferative genes. Direct inhibition of NF-κB DNA binding activity (less common).