الفهرس 
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Abstract
The NF-κB transcription factor family represents an important group of regulators of a broad range of genes involved in cellular responses to inflammatory and stress signals. Knockout mouse studies have also revealed a key role for this family in broad physiological processes, including immune function and metabolism. Although some redundancy in the function of members of this family exists, there is a surprising degree of specificity in the role of each transcriptional complex in gene transcription and physiological function. Each NF-κB complex displays distinct affinities for the different DNA binding sites present in the promoters of NF-κB-regulated genes, and this may contribute to some of the specificity exhibited. The identification of specific components of the NF-κB signal transduction pathway provides an opportunity to define mechanisms at the biochemical level by which specific members of the NF-κB family are activated. Coordinated and timely control of transcription-factor activities is crucial to cell survival and development. Both deletion and hyperactivity of NF-κB have severe consequences for systemic responses. It is fair to say that the IκB proteins represent one of the primary means of NF-κB regulation, although their versatile effects on NF-κB activity make them more complex than simple inhibitory proteins. A diverse array of post translational modifications of IKK, IκB, and NF-κB proteins provide the means to fine tune the NF-κB response at multiple levels. Protein–protein interactions of the NF-κB subunits with other isoforms, co-activators and other transcriptional factors are the key to NF-κB specificity. These interactions are controlled via different signalling pathways through activation and phosphorylation of components of transactivation complexes. The interactions of these components in enhanceosomes provide specific control over target gene expression. Although the inhibition of NF-κB has been shown to reduce the clinical phenotypes in some disease states, it may not, however, be logical to block the activation of NF-κB for prolonged periods since it plays such a critical part in the immune and other defense responses. Because the full transcriptional activation of NF-κB involves the crosstalk with other signal pathways which involve protein kinase A, phosphatidyl inositol 3 kinase/Akt and mitogen-activated protein kinases, blocking the activity of these kinases also provide alternative strategy to regulate the NF-κB activity. Furthermore, modulating the expression of specific target genes can also be used as a potential approach for the management of NF-κB related diseases. The transcription factors of the NF-κB family control the expression of a large number of target genes in response to changes in the environment, thereby helping to orchestrate inflammatory and immune responses. whereas maintenance of appropriate levels of NF-κB activity is a critical factor in immune system development and normal cellular proliferation, constitutive NF-κB activation is likely involved in the pathogenesis of several diseases. Regulation and control of NF-κB activation can be a powerful therapeutic strategy for inhibiting tumor growth and viral infections and for reducing the tissue damage that follows the release of inflammatory mediators, therefore more studies will be required to develop NF-κB specific and cell type specific drugs that can inhibit NF-κB activation only in target cells to be used in the treatment of diseases in which the NF-κB system is dysregulated.