NF-kB (nuclear factor kB) is sequestered in the cytoplasm by IkB family of inhibitory proteins that mask the nuclear localization signal of NF-kB thereby preventing translocation of NF-kB to the nucleus (1). External stimuli such as tumor necrosis factor or other cytokines results in phosphorylation and degradation of IkB releasing NF-kB dimers. NF-kB dimer subsequently translocates to the nucleus and activates target genes. Synthesis of IkBa is autoregulated (2). IkB proteins are phosphorylated by IkB kinase complex consisting of at least three proteins, IKK1/a, IKK2/b, and IKK3/g (3-5). IKK1/a and IKKbeta are phosphorylated by NF-kB-inducing kinase (NIK) (6) and MAP kinase kinase kinase-1 (MEKK1) (7), respectively. Recent studies have shown that IKKbeta, not IKK1/a, is the target proinflammatory stimuli (9). Targeted disruption of IKKbeta gene in mice also results in extensive liver damage from apotopsis and death as embryo (9).
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