NDLI: An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.

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An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Driggers, P. H. Levi, B. Z. Ozato, K. Gleason, S. L. Mak, W. H. Appella, E. Marks, M. S. Flanagan, J. R. Ennist, D. L.
Description	Author Affiliation: Driggers PH ( Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.);
Abstract	Interferons (IFNs) induce transcription of major histocompatibility complex (MHC) class I genes through the conserved IFN consensus sequence (ICS) that contains an IFN response motif shared by many IFN-regulated genes. By screening mouse lambda ZAP expression libraries with the ICS as a probe, we isolated a cDNA clone encoding a protein that binds the ICS, designated ICSBP. Protein blot analysis with labeled oligonucleotide probes showed that ICSBP binds not only the MHC class I ICS but also IFN response motifs of many IFN-regulated genes, as well as a virus-inducible element of the IFN-beta gene. The ICSBP cDNA encodes 424 amino acids and a long 3' untranslated sequence. The N-terminal 115 amino acids correspond to a putative DNA-binding domain and show significant sequence similarity with other cloned IFN response factors (IRF-1 and IRF-2). Because of the structural similarity and shared binding specificity, we conclude that ICSBP is a third member of the IRF gene family, presumably playing a role in IFN- and virus-mediated regulation of many genes. Although IRF-1 and IRF-2 share some similarity in their C-terminal regions, ICSBP shows no similarity to IRF-1 or IRF-2 in this region, suggesting that it is more distantly related. We show that ICSBP mRNA is expressed predominantly in lymphoid tissues and is inducible preferentially by IFN-gamma. The induction by IFN-gamma appears to be predominant in lymphocytes and macrophages, implying that ICSBP plays a regulatory role in cells of the immune system. The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	10
Volume Number	87
Language	English
Publisher	National Academy of Sciences
Publisher Date	1990-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carrier Proteins Genetics DNA-Binding Proteins Enhancer Elements, Genetic Genes, MHC Class I Interferon-gamma Pharmacology Repressor Proteins Transcription Factors Amino Acid Sequence Animals Animals, Newborn DNA Probes Drug Effects Gene Library Immunoblotting Interferon Regulatory Factors Liver Immunology Mice Molecular Sequence Data Recombinant Proteins Sequence Homology, Nucleic Acid Spleen Comparative Study Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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