Activation and repression of the 2-5A synthetase and p21 gene promoters by IRF-1 and IRF-2 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-03

AUTHORS

Eliana M Coccia, Nicoletta Del Russo, Emilia Stellacci, Roberto Orsatti, Eleonora Benedetti, Giovanna Marziali, John Hiscott, Angela Battistini

ABSTRACT

The Interferon Regulatory Factors-1 and -2 (IRF-1 and IRF-2) were originally identified as transcriptional regulators of the interferon (IFN) and IFN-stimulated genes. These factors also modulate immune response and play a role in cell growth regulation. In this study we analysed the effect of the ectopic expression of IRF-1 and IRF-2 on the regulation of two potential IRF target genes involved in cell growth regulation, 2-5A synthetase and p21 (WAF/CP1), both of which contain consensus binding sites for IRF family members within their promoters. Following ectopic expression, IRF-1 transactivated 2-5A synthetase and p21 genes, an effect that was counterbalanced by concomitant ectopic expression of IRF-2. These effects were mediated by direct binding of IRF to the gene promoters. A construct expressing an IRF-2 antisense (FRI-2) was able to revert the inhibitory effect of IRF-2 on the IRF-1 transactivation. IRF-1 also induced expression of its homologous repressor IRF-2 as indicated by EMSA analysis using an IRF-E probe from the IRF-2 promoter; and by cotransfection of IRF-1 together with an IRF-2 promoter CAT construct. Therefore, the induction of IRF-1 by IFNs or other stimuli acts as a transactivator of genes involved in cell growth regulation, as well as of its own repressor IRF-2, thus providing autoinhibitory regulation of IRF-1 activated genes. More... »

PAGES

1202536

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1202536

DOI

http://dx.doi.org/10.1038/sj.onc.1202536

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1013383186

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10321737


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