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

Abstract

Interferon regularory factor 1 (IRF-1) is a DNA-bindlng factor which recognizes regulatory elements In the promoters of Interferon (IFN)-β 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-β 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. © 1993 Oxford University Press.