Interferon regulatory factors: growth control and histone gene regulation - it's not just interferon anymore

Abstract

Interferon-regulatory factors (IRFs) are a related family of proteins originally identified by their ability to bind a DNA sequence found in the beta-interferon gene and many interferon-stimulated genes. Two well-studied members of this family, IRF-1 and IRF-2, have antagonistic roles in interferon-beta gene regulation: IRF-1 activates this gene, and IRF-2 represses the activation by IRF-1, IRF-1 and IRF-2 have more recently been linked to growth control by displaying tumor suppressor and oncogenic activities, respectively. A possible explanation for the oncogenic activity of IRF-2 is the discovery that IRF-2 can activate a histone gene that is functionally coupled to cell cycle progression. This first report of native IRF-2 playing the role of activator of a gene essential for growth may lead to the discovery of a more general involvement of interferon regulatory factors in mediating growth control.

Inhibition of Inducible Nitric Oxide Synthase Expression by Interferons α and β in Bovine Retinal Pigmented Epithelial Cells

“…It would be consistent to propose that IFN-␣, by increasing IRF-2 mRNA and decreasing IRF-1 mRNA accumulation, could favor the neosynthesis of the repressor IRF-2, which is more stable than IRF-1 (43). As previously suggested, IRF-1 and IRF-2 could compete for the specific ISRE sequence (31,40). Then, the accumulation of IRF-2 and diminution of IRF-1 could favor the interaction of IRF-2 with the NOS-2 gene promoter in place of IRF-1 and could suppress the activation of NOS-2 gene by IRF-1, after IFN-␣ treatment.…”

“…They demonstrated that IFN-␣ could suppress the IFN-␥-induced interferon consensus sequence binding protein mRNA accumulation in peritoneal macrophages. Besides these interferoninduced transcription factors, there is another transcription factor, termed IRF-2, that is structurally similar to IRF-1, but that represses the effect of IRF-1 (31,40). We demonstrated that IRF-2 mRNA is differentially regulated by the IFNs, since IFN-␥ largely decreased its accumulation, while IFN-␣ significantly increased it.…”

CXCR4/CXCL12 expression and signalling in kidney cancer

“…IRF-1 functions as a regulator of the interferon system and key transcription factor in the regulation of cell cycle and apoptosis. It has been demonstrated to have antiproliferative and tumour suppressive functions, particularly through its transcriptional activation of IFN-a and IFN-b (Vaughan et al, 1997;Um et al, 2000). rhCXCL12a also has an interesting but transient (i.e.…”

The Tumor Suppressor Interferon Regulatory Factor 1 Interferes with SP1 Activation to Repress the Human CDK2 Promoter

“…Interferon regulatory factors (IRFs) 1 are activated by the anti-proliferative actions of interferons through JAK/STATmediated signaling mechanisms to inhibit cell growth (1)(2)(3).…”