NF-kB is silenced in the cytoplasm by an inhibitory protein, IkB (1). 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 (3-6). 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. Six members of IkB family members have been identified (1). One of the first gene induced following NF-kB activation is IkBa.
1. Sanjo H, Kawai T, and Akira S. DRAKs, novel serine/threonine kinases related to death associated protein kinase that trigger apoptosis. J Biol Chem 273 (44): 29066-29071, 1998.
2. Matsumoto M, Takeda K, Sanjo H, and Akira S. ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Mol Cell Biol 18 (3): 1642-1651, 1998.
3. Verma, I.M., Genes. Dev. 9: 2723-2735, 1995.
4. Verma, I. And Stevenson, J.K. Proc. Nat. Acad. Sci USA 94: 11758 (1997).
5. DiDonato, J.A., et al. Nature 388: 548- (1997).
6. Regnier, C.H., et al. Cell 90, 373 (1997).
7. Mercurio, F., et al. Science 278: 860 (1997).
8. Yamaoka, S., et al. Cell 93: 1231-1240 (1998).