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PMID: 1901265 Published · ppublish English Journal Article

Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor.

The EMBO journal ·Vol. 10 ·No. 4 ·1991-04-00 ·Pages 927-32

Decker T, Lew DJ, Mirkovitch J, Darnell JE

Abstract

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.

MeSH Terms
Base Sequence Cell Line Cytochalasin B/pharmacology DNA-Binding Proteins/metabolism Exodeoxyribonucleases Fibroblasts/drug effects,metabolism GTP-Binding Proteins/biosynthesis,genetics Gene Expression Regulation/drug effects HeLa Cells/drug effects,metabolism Humans Interferon-gamma/metabolism,pharmacology Kinetics Molecular Sequence Data Plasmids Promoter Regions, Genetic Recombinant Proteins Transcription, Genetic/drug effects
Chemicals
DNA-Binding Proteins Recombinant Proteins Cytochalasin B Interferon-gamma Exodeoxyribonucleases exodeoxyribonuclease III GTP-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Decker T
Rockefeller University, New York, NY 10021.
Lew D J
Mirkovitch J
Darnell J E
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-04-00
Pages
927-32
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452736
Subset
IM
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