title: Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes.
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.
authors.affiliation: Genetics of Eukaryotes, GBF--Gesellschaft für Biotechnologische Forschung mbH, Braunschweig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kirchhoff
authors.forename: F
authors.initials: F
authors.lastname: Schaper
authors.forename: H
authors.initials: H
authors.lastname: Hauser
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016899:Interferon-beta; D004247:DNA