Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor.
We have investigated events following treatment of cells with interferon-gamma (IFN-gamma) that lead to the immediate transcriptional activation of an inducible gene. A gamma-interferon activation factor (GAF) was activated in the cytoplasm of human fibroblasts immediately after IFN-gamma treatment and bound to a newly identified target DNA sequence, the gamma-interferon activation site (GAS). The time course of activation of GAF was different in fibroblasts and HeLa cells and correlated well with IFN-gamma-induced transcriptional activation in both cell types. IFN-gamma-dependent activation of GAF also occurred in enucleated cells (cytoplasts), showing that an inactive cytoplasmic precursor is converted to the active factor. These findings support the concept that ligand-specific signals originating at the cell surface are transmitted through latent cytoplasmic proteins which are activated to bind specific DNA sites and then move to the nucleus to activate the transcription of specific sets of genes.
Decker
T
T
Rockefeller University, New York, NY 10021.
Lew
D J
DJ
Mirkovitch
J
J
Darnell
J E
JE
D001483:Base Sequence; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D003571:Cytochalasin B; D007371:Interferon-gamma; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III; D019204:GTP-Binding Proteins