Selectivity of the NF-kB response

NF-kB is activated by many stimuli and NF-kB binding sites have been identified in a wide variety of genes. Yet, NF-kB-dependent gene expression must be stimulus- and cell-type-specific. In others words, the cellular response to different NF-kB activating stimuli, such as TNFa, 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-kB-inducing stimulus must also be different. Finally, kinetics of gene expression must be accounted for, so that all NF-kB-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-kB-dependent gene expression have been analyzed because they are likely to form the basis for physiological responses. NF-kB was first reported in 1986 as a DNA-binding protein that recognizes, in a DNA sequence-specific manner, an important motif within the intronic enhancer of the immu-noglobulin (Ig) k light chain gene (Sen and Baltimore 1986). NF-kB DNA-binding activit