Interferon-stimulated gene factor 3 complex (ISGF3) (ISGF3)

The Interferon-stimulated gene factor 3 (ISGF3) complex is a heterotrimeric transcription factor that serves as the primary effector of Type I and Type III interferon (IFN) signaling (Schindler et al., Science, 1992). It consists of Signal Transducer and Activator of Transcription 1 (STAT1), Signal Transducer and Activator of Transcription 2 (STAT2), and Interferon Regulatory Factor 9 (IRF9) (UniProt: P42224, P52630, Q00610). Following the activation of IFN receptors and subsequent phosphorylation of STAT proteins by Janus kinases (JAKs), the complex assembles in the cytoplasm and translocates to the nucleus. Once inside, ISGF3 binds to Interferon-Stimulated Response Elements (ISRE) to drive the expression of a vast array of Interferon-Stimulated Genes (ISGs) that mediate antiviral, pro-apoptotic, and anti-proliferative effects (Platanias, Nat Rev Immunol, 2005). Dysregulation of the ISGF3 complex is implicated in various conditions, including chronic viral infections, autoimmune diseases like systemic lupus erythematosus, and several types of cancer. Pharmacological modulation of ISGF3 is achieved either through the administration of exogenous interferons to stimulate its activity or via JAK inhibitors to suppress its formation in inflammatory contexts (DrugBank: DB06016, DB00105).

Other names

STAT1-STAT2-IRF9 complexISGF-3Interferon-stimulated transcription factor 3TIF-1

Assembly of phosphorylated STAT1, STAT2, and IRF9 into a heterotrimer that translocates to the nucleus to bind interferon-stimulated response elements (ISRE) and initiate transcription of antiviral and immunomodulatory genes (Platanias, Nat Rev Immunol, 2005; UniProt: P42224, P52630, Q00610).