Nuclear factor kappa-light-chain-enhancer of activated B cells and Inhibitor of nuclear factor kappa-B kinase complex (NF-κB/IKK complex)

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) complex and its upstream regulator, the Inhibitor of nuclear factor kappa-B kinase (IKK) complex, constitute a central signaling axis in human biology (Zhang et al., 2017). NF-κB is a family of inducible transcription factors that regulate genes involved in immunity, inflammation, and cell survival. In its inactive state, NF-κB is sequestered in the cytoplasm by IκB inhibitory proteins. Upon stimulation by various stimuli such as cytokines or pathogens, the IKK complex (comprising IKKα, IKKβ, and NEMO) phosphorylates IκB, marking it for ubiquitination and proteasomal degradation (Hacker and Karin, 2006). This release allows NF-κB to translocate to the nucleus and initiate gene transcription. Dysregulation of this pathway is a hallmark of many chronic inflammatory diseases and various cancers, where it promotes tumor cell proliferation and resistance to apoptosis (Baud and Karin, 2009). Consequently, the NF-κB/IKK axis is a major therapeutic target, with drugs like proteasome inhibitors and IKK-specific inhibitors designed to modulate its activity.

Other names

NF-kappaBNFKBIkappaB kinaseIKK complexIκB kinaseRel protein complexIKK/NF-kappaB signaling axis

Inhibition of the IKK complex prevents the phosphorylation and subsequent degradation of IκB proteins, thereby sequestering NF-κB in the cytoplasm and preventing its transcriptional activity (Hacker and Karin, 2006). Other agents, such as proteasome inhibitors (e.g., Bortezomib), prevent the degradation of phosphorylated IκB, while some drugs directly interfere with NF-κB DNA binding or nuclear translocation (Baud and Karin, 2009).