O15111

The transcription factor NFkB is retained in the cytoplasm in an inactive form by the inhibitory protein IkB. Activation of NFkB requires that IkB be phosphorylated on specific serine residues, which results in targeted degradation of IkB. IkB kinase α (IKKα), previously designated CHUK, interacts with IkB-α and specifically phosphorylates Iκβ-α on Serine 32 and 36, the sites that trigger its degradation. IKKα appears to be critical for NFkB activation in response to proinflammatory cytokines. Phosphorylation of IkB by IKKα is stimulated by the NFkB inducing kinase (NIK), which itself is a central regulator for NFkB 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 IkB phosphorylation.