NF-kappaB is activated by many stimuli and NF-kappaB binding sites have been identified in a wide variety of genes. Yet, NF-kappaB-dependent gene expression must be stimulus- and cell-type-specific. In others words, the cellular response to different NF-kappaB activating stimuli, such as TNFalpha, IL-1, and LPS, must be different; and the response of different cell types, such as lymphocytes, fibroblasts, or epithelial cells, to the same NF-kappaB-inducing stimulus must also be different. Finally, kinetics of gene expression must be accounted for, so that all NF-kappaB-dependent genes are not activated simultaneously even if cell type and stimulus are constant. Here, we explore the mechanistic framework in which such regulatory aspects of NF-kappaB-dependent gene expression have been analyzed because they are likely to form the basis for physiological responses.
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