The transcription factor NFκB is retained in the cytoplasm in an inactive form
by the inhibitory protein IκB. Activation of NFκB requires that IκB be phosphorylated
on specific serine residues, which results in targeted degradation
of IκB. IκB kinase α (IKKα), previously designated CHUK, interacts with IκBα
and specifically phosphorylates IκBα on Serine 32 and 36, the sites that
trigger its degradation. IKKα appears to be critical for NFκB activation in
response to proinflammatory cytokines. Phosphorylation of IκB by IKKα is
stimulated by the NFκB inducing kinase (NIK), which itself is a central regulator
for NFκB activation in response to TNF and IL-1. The functional IKK complex
contains three subunits, IKKα, IKKβ and IKKγ (also designated NEMO),
and each appear to make essential contributions to IκB phosphorylation.