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pubmed:abstractText |
The NF kappa B transcription factor exists in an inactive state when complexed with I kappa B alpha in the cytosol. Upon stimulation by a variety of agents, NF kappa B is released from I kappa B alpha and is translocated to the nucleus to induce kappa B motif-containing promoters. Once I kappa B alpha is dissociated from NF kappa B, I kappa B alpha is rapidly degraded. Few studies have been reported concerning the molecular basis for the regulation of I kappa B alpha gene expression. The current studies now show: (1) the expression of I kappa B alpha can be induced by protein synthesis inhibitors including cycloheximide, anisomycin, and puromycin; (2) cycloheximide-dependent induction can be blocked by a transcriptional inhibitor; (3) double-stranded RNA and tumor necrosis factor alpha, which are both known to induce NF kappa B, induce the expression of I kappa B alpha, whereas L-cysteine, which is known to inhibit NF kappa B expression, inhibits I kappa B alpha expression; and (4) the induction of I kappa B alpha gene expression is transient, as is the induction of other NF kappa B-inducible genes. These findings suggest that I kappa B alpha is a NF kappa B-inducible gene. The current results also show a concomitant induction of both subunits of NF kappa B (p50 and p65) after the treatment of cells with double-stranded RNA. Based on these results, a model is proposed suggesting the existence of integrated pathways for the positive and negative autoregulation of I kappa B alpha and NF kappa B.
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