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Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). [1] Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. [2]
IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation. [11] The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK. [12] IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals. [13]
IRF3 is a member of the interferon regulatory transcription factor (IRF) family. [5] IRF3 was originally discovered as a homolog of IRF1 and IRF2.IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a DNA-binding domain, a C-terminal IRF association domain and several regulatory phosphorylation sites. [6]
Interferon regulatory factor 8 (IRF8) also known as interferon consensus sequence-binding protein (ICSBP), is a protein that in humans is encoded by the IRF8 gene. [5] [6] [7] IRF8 is a transcription factor that plays critical roles in the regulation of lineage commitment and in myeloid cell maturation including the decision for a common myeloid progenitor (CMP) to differentiate into a ...
IRF4 is a transcription factor belonging to the Interferon Regulatory Factor (IRF) family of transcription factors. [8] [9] In contrast to some other IRF family members, IRF4 expression is not initiated by interferons; rather, IRF4 expression is promoted by a variety of bioactive stimuli, including antigen receptor engagement, lipopolysaccharide (LPS), IL-4, and CD40.
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially described as a transcription factor able to activate expression of the cytokine Interferon beta, [6] IRF-1 was subsequently shown to function as a transcriptional activator or repressor of a variety of target genes.
The IRF7 pathway was shown to be silenced in some metastatic breast cancer cell lines, which may help the cells avoid the host immune response. [7] Restoring IRF7 to these cell lines reduced metastases and increased host survival time in animal models.
After recognizing viral DNA, DNA sensors initiate the downstream signaling pathways by activating STING-mediated interferon response. [15] Adenovirus, herpes simplex virus, HSV-1 and HSV-2, as well as the negative-stranded RNA virus, vesicular stomatitis virus (VSV), have been shown to be able to activate a STING-dependent innate immune ...