IFN-alpha super-induction of HLA class I expression by a variant thymoma cell line involves nuclear translocation of Rel complexes.
Variant thymoma lines have been described which exhibit a substantially increased level of HLA class I induction by IFN-alpha, but not by IFN-gamma, and an unchanged response of other IFN-alpha-stimulated genes (Burrone et al., EMBO J. 1985. 4: 2855-2860). We report that their amplified response correlates with the nuclear translocation of Rel transcription factors upon prolonged treatment with IFN-alpha. The variant cells contain an IkappaBalpha subset with a significantly shortened half-life, and a constitutively active form of IkappaBalpha efficiently blocks HLA class I induction. Therefore, in addition to STAT-mediated induction, prolonged exposure to IFN-alpha can affect transcription involving Rel factors, which are implicated in the regulation of numerous immune response and viral genes.
Travers
H
H
CCRIS, The Medical School, University of Birmingham, GB.
Girdlestone
J
J
D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D020672:I-kappa B Proteins; D016898:Interferon-alpha / Q000494:pharmacology*; D008025:Ligases / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D013945:Thymoma / Q000276:immunology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D020672:I-kappa B Proteins; D016898:Interferon-alpha; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D000072000:NF-KappaB Inhibitor alpha; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases