How NF-κB is activated: the role of the IκB kinase (IKK) complex

Rel/NF-κB transcription factors are primarily regulated by association with inhibitor IκB proteins. Thus, in most cells NF-κB exists in the cytoplasm in an inactive complex bound to IκB. Most agents that activate NF-κB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IκB. The key regulatory step in this pathway involves activation of a high molecular weight IκB kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKKα and IKKβ subunits. This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.