Coordinate induction of I kappa B alpha and NF kappa B genes.
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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Department of Pathology, University of Tennessee Medical Center, Memphis 38163.
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Scott
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D000595:Amino Acid Sequence; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D005809:Genes, Regulator; D020672:I-kappa B Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D011691:Puromycin; D012313:RNA; D000841:Anisomycin; D004247:DNA; D003513:Cycloheximide; D003545:Cysteine