Figure 3.

IFN-dependent and -independent ISG transcription mediated by IRF1. According to the current state of knowledge, expression of IRF1 is driven by homodimers of STAT1 (GAF), as well as STAT1/STAT2 heterodimers, recognizing a single GAS sequence in the IRF1 promoter. Recent studies confirmed that basal expression of IRF1 can be detected in many cell types under basal conditions. Moreover, binding of IRF1 to ISRE-containing genes can play a role in maintaining constitutive expression of certain group of ISGs (left panel). After IFN-I or IFN-II stimulation GAF and GAF-like (STAT1/STAT2 heterodimers) complexes are rapidly formed and translocated to the nucleus to initiate IRF1 expression. Subsequently, IRF1 as an additional abundant transcription factor can collaborate with ISGF3 and GAF complexes stimulating ISRE-containing genes, thus appearing as an important link between IFN-I and IFN-II responses. Abbreviations: IFN, interferon; STAT, signal transducer and activator of transcription; IRF, interferon regulatory factor; JAK, Janus kinase; TYK, tyrosine kinase; ISGF3, interferon-stimulated gene factor 3; GAF, γ-activated factor; ISRE, interferon-stimulated response element; GAS, γ-activated sequence; ISG, interferon-stimulated gene; P, phosphate.