How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex

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