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, such as IL-1 results in phosphorylation and degradation of IkB releasing NF-kB dimers.
NF-kB dimer subsequently translocates to the nucleus and activates target genes (2).
Recently, Li et al.
(3) have isolated a cDNA coding for a protein named Act1 (NFkB activator 1).
Act1/CIKS cDNA codes for a protein containing 574aa with a predicated molecular mass of 60kD.
Act1/CIKS protein contains a helix-loop-helix domain in its N-terminal portion and a coiled-coil structure at the C terminus.
Act1 lacks any catalytic domain, however, it activates IKK through the helix-loop-helix domain.
The activation of NF- B by Act1 appears to be through the NIK-IKK complex, because a NIK dominant-negative mutant protein inhibited Act1-induced NF- B activation.
IL-1 responsive pathway is also necessary for Act1 function.
Act1 mRNA is expressed in a variety of tissues, with high level in thymus, kidney and placenta; moderate level in heart, skeletal muscle, colon, liver, lung and small intestine; and at a very low level in brain, spleen, and peripheral blood leukocytes.
