Nucleic Acids Research, 1993, Vol. 21, No. 12 2881-2889
© 1993
MOLECULAR BIOLOGY |
Interferon regulatory factor 1 (IRF-1) mediates cell growth inhibition by transactivation of downstream target genes
Genetics of Eukaryotes, GBF—Gesellschaft für Biotechnologische Forschung mbH Mascheroder Weg 1, D-3300 Braunschweig, Germany
*To whom correspondence should be addressed
Received February 25, 1993. Revised April 29, 1993. Accepted April 29, 1993.
Interferon regularory factor 1 (IRF-1) is a DNA-bindlng factor which recognizes regulatory elements In the promoters of Interferon (IFN)-ß and some IFN-Inducible genes. We observed that expression of transfected murlne 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-ß 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-bindlng 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.
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