Transcriptional Regulation of Interferon-stimulated Genes: A DNA Response Element and Induced Proteins That Recognize It

Human type I interferons (IFN-α and IFN-β) are a family of moderately related polypeptides that bind a single cell-surface receptor on most (if not all) human nucleated cells. Cells treated with IFN respond by a profound alteration of their metabolic profile, including cessation of cellular proliferation and induction of the antiviral state. RNA transcription and protein synthesis are necessary to bring about these metabolic changes, with perhaps 10–15 genes being involved in the immediate response, as judged from two-dimensional gel electrophoresis of [35S]methionine-labeled proteins (Knight and Korant 1979). One of the earliest responses to IFN treatment, which is detectable within minutes of IFN addition, is the transcriptional activation of a set of previously quiescent genes (Friedman et al. 1984; Larner et al. 1984; Friedman and Stark 1985). Various laboratories working on IFN have identified some nine different human genes transcriptionally activated by IFN (Friedman et al. 1984; Larner et al....