The NF-kappaB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IkappaB proteins (1-3). Most agents that activate NF-kappaB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IkappaB (3-7). 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 three tightly associated IKK subunits.
