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  • Title: Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.
    Author: Weisz A, Marx P, Sharf R, Appella E, Driggers PH, Ozato K, Levi BZ.
    Journal: J Biol Chem; 1992 Dec 15; 267(35):25589-96. PubMed ID: 1460054.
    Abstract:
    The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.
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