Kinetically coordinated induction of TAP1 and HLA class I by IFN-gamma: the rapid induction of TAP1 by IFN-gamma is mediated by Stat1 alpha.
Transporter associated with Ag processing-1 (TAP1) is induced by IFN-gamma more rapidly than is HLA class I. Kinetic analysis of transfectants reveals that IFN-gamma activates the TAP1 promoter more rapidly than the HLA-B7 class I promoter. A gamma-activating sequence (GAS) in the TAP1 promoter is necessary for the rapid induction by IFN-gamma. Two overlapping IFN consensus sequences contribute to the constitutive and TNF-induced expression of TAP1 but are not necessary for the IFN-gamma response. Moreover, IFN-gamma activates the GAS-binding protein Stat1 alpha much more rapidly than it induces the IFN consensus sequence-binding protein IRF-1, which mediates the response of the HLA-B7 class I promoter. We conclude that IFN-gamma uses different transcription factors to regulate the sequence of appearance of these interacting gene products.
Min
W
W
Department of Pathology, Yale Medical School, New Haven, CT 06511, USA.
Pober
J S
JS
Johnson
D R
DR
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000187:drug effects; D015235:HLA-B Antigens / Q000096:biosynthesis; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D006680:HLA Antigens; D015235:HLA-B Antigens; C035270:HLA-B5 antigen; D015395:Histocompatibility Antigens Class I; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D046911:Macromolecular Substances; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; D014157:Transcription Factors; C079868:gamma interferon activation factor; C071313:LMP-2 protein; D007371:Interferon-gamma; D010450:Endopeptidases; D003546:Cysteine Endopeptidases