Interferon-stimulated gene factor 3 complex (ISGF3)

The Interferon-stimulated gene factor 3 complex (ISGF3) is a multi-subunit transcription factor essential for mediating the cellular response to type I interferons (IFN-α/β). ISGF3 is composed of phosphorylated STAT1, STAT2, and IRF9 (also known as p48). Upon IFN receptor stimulation, JAK kinases phosphorylate STAT1 and STAT2, which dimerize and recruit IRF9 to form ISGF3 in the cytoplasm. The complex translocates to the nucleus and binds to interferon-stimulated response elements (ISRE) in DNA, activating the transcription of a broad set of antiviral and immunomodulatory genes known as interferon-stimulated genes (ISGs)[2]. ISGF3 activity is central to antiviral immunity, but its dysregulation is linked to autoimmunity and certain cancers. No approved therapeutics directly target ISGF3 itself, but modulation of its upstream regulators (interferons, JAK kinases) is clinically important for managing viral infections, cancers, and autoimmune diseases[2].

Other names

ISGF3Interferon-stimulated gene factor 3Interferon-stimulated gene factor 3 transcription complex

Activation: Interferons bind their receptors and activate JAK-STAT signaling, leading to ISGF3 formation and nuclear translocation[2]. Inhibition: JAK inhibitors block phosphorylation of STAT1 and STAT2, thus preventing ISGF3 assembly and ISG expression.