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PMID: 8332497 Published · ppublish English Journal Article

Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes.

Nucleic acids research ·Vol. 21 ·No. 12 ·1993-06-25 ·Pages 2881-9

Kirchhoff S, Schaper F, Hauser H

Abstract

Interferon regulatory factor 1 (IRF-1) is a DNA-binding factor which recognizes regulatory elements in the promoters of interferon (IFN)-beta and some IFN-inducible genes. We observed that expression of transfected murine IRF-1 in different mammalian cell lines leads to down-regulation or stop of proliferation depending on the extent of expression. Expression of fusion proteins composed of IRF-1 and the hormone binding domain of the human estrogen receptor does not exhibit IRF-1 activity in the absence of estrogen. However, after estrogen treatment of the cells IFN-beta promoters are activated and the cells stop growing. As shown by expression of IRF-1 mutants both functions of the IRF-1-protein require DNA-binding and transcriptional activation. Since secreted factors including IFNs are not responsible for the anti-proliferative effect of IRF-1 we suggest that IRF-1 may be regarded as a negative regulator of cell growth which acts by activation of down-stream effector genes.

MeSH Terms
Animals Cell Division/genetics Cell Line DNA/metabolism DNA-Binding Proteins/genetics,physiology Gene Expression Humans Interferon Regulatory Factor-1 Interferon-beta/genetics Mice Phosphoproteins/genetics,physiology Receptors, Estrogen/genetics Recombinant Fusion Proteins/metabolism Transcription Factors/physiology Transcriptional Activation Transfection
Chemicals
DNA-Binding Proteins IRF1 protein, human Interferon Regulatory Factor-1 Irf1 protein, mouse Phosphoproteins Receptors, Estrogen Recombinant Fusion Proteins Transcription Factors Interferon-beta DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kirchhoff S
Genetics of Eukaryotes, GBF--Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany.
Schaper F
Hauser H
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.12.2881
Published
1993-06-25
Pages
2881-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC309674
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/21.12.2881 PMC Full Text View journal details
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