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  • 1
    Publication Date: 2001-07-14
    Description: Interferons (IFN) alpha/beta and gamma induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dupuis, S -- Dargemont, C -- Fieschi, C -- Thomassin, N -- Rosenzweig, S -- Harris, J -- Holland, S M -- Schreiber, R D -- Casanova, J L -- New York, N.Y. -- Science. 2001 Jul 13;293(5528):300-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Humaine des Maladies Infectieuses, Universite de Paris Rene Descartes-INSERM UMR550, Faculte de Medecine Necker-Enfants Malades, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11452125" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Line ; Child ; Child, Preschool ; DNA/metabolism ; DNA-Binding Proteins/genetics/*physiology ; Female ; Fibroblasts/metabolism/virology ; Gene Expression Regulation ; *Germ-Line Mutation ; Humans ; *Immunity/genetics ; Interferon-Stimulated Gene Factor 3 ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; Interferon-alpha/*immunology/metabolism ; Interferon-gamma/*immunology/metabolism ; Janus Kinase 1 ; Mice ; Mycobacterium Infections/genetics/*immunology ; Mycobacterium avium Complex/immunology ; Mycobacterium avium-intracellulare Infection/genetics/immunology ; Mycobacterium bovis ; Pedigree ; Protein Binding ; Protein-Tyrosine Kinases/genetics ; STAT1 Transcription Factor ; Signal Transduction ; Simian virus 40 ; Trans-Activators/genetics/*physiology ; Transcription Factors/physiology ; Virus Diseases/genetics/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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