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Screening for Inhibitors of Transcription Factors Using Luciferase Reporter Gene Expression in Transfected Cells

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Nuclear transcription factors (TF) regulate tissue- and stimulus-specific gene expression through their ability to integrate extracellular signals at the level of the nucleus (1 ). Multiple human diseases, including cancer, cardiovascular disease, neurologic and autoimmune disorders, result from aberrations in the expression of genes regulated by these transcription factors (2 ). Interest in the exploitation of transcription factors for the development of gene-regulating therapeutics has grown steadily over the past few years. The ability to modulate abnormal gene expression through manipulation of TF function offers an innovative approach to disease therapies. TF modulation holds particular promise in diseases where several proteins contribute simultaneously to the pathology, such as in autoimmune disease, where a plethora of cytokines, destructive enzymes, and cell-adhesion molecules combine to enhance disease progression.
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