The enzyme IκB kinase (IKK) stimulates phosphorylation of two serine residues in the regulatory domain of Inhibitor of kappa B (IκB), targetting the IκB molecules for ubiquitin/proteasome degradation, and releasing NF-κB from inhibition as cytoplasm-sequestered NF-κB dimers.
Many tumor types have chronically active NF-κB, resulting from:
● mutations in genes encoding the NF-κB transcription factors themselves, or
● mutations in genes that control NF-κB activity
Several viruses, including HIV/AIDS, control the expression of viral genes through viral binding sites for NF-κB, thus contributing to viral replication or viral pathogenicity. For HIV-1, activation of NF-κB could be related to activation of the virus from a latent, inactive state.