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

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling axis is a central regulator of the immune response, inflammation, and cell survival (Oeckinghaus & Ghosh, 2009). It consists of a family of transcription factors—including p50, p52, RelA (p65), RelB, and c-Rel—that remain sequestered in the cytoplasm by inhibitor of κB (IκB) proteins under resting conditions (Zhang et al., 2017). Activation occurs via the canonical or non-canonical pathways, typically involving the IκB kinase (IKK) complex, which triggers the degradation of IκB and allows NF-κB to translocate to the nucleus to drive gene expression (Liu et al., 2017). Chronic overactivation of this axis is a hallmark of many inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, as well as various malignancies where it promotes tumor growth and resistance to apoptosis (Taniguchi & Karin, 2018). Consequently, the NF-κB axis is a major therapeutic target, with drugs like proteasome inhibitors (e.g., Bortezomib) and glucocorticoids currently in clinical use, while more specific IKK inhibitors continue to be explored in clinical development (Liu et al., 2017).

Other names

NF-kappaB pathwayNF-kB signaling pathwayNuclear factor-kappa B pathwayRel transcription factor signaling

Inhibition of the IκB kinase (IKK) complex, prevention of IκBα proteasomal degradation, inhibition of NF-κB nuclear translocation, and interference with NF-κB DNA binding activity (Liu et al., 2017; Zhang et al., 2017).