Fig. 8
From: A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription
Model of the molecular switch from resting to IFN-induced gene expression. Under homeostatic conditions, a tonic signal from the type I-IFN receptor activates small quantities of ISGF3, which increase basal expression of the genes encoding the ISGF3 subunits STAT1, STAT2, and IRF9. This causes the constitutive formation of STAT1–STAT2 as well as STAT2–IRF9 complexes. Basal expression of a large fraction of interferon-induced genes (ISGs) is stimulated by STAT2–IRF9 complexes that appear in the nucleus without a signaling requirement. Signaling by the type I-IFN receptor and to a significant extent also by the IFN-γ receptor causes the formation of tyrosine-phosphorylated STAT1–STAT2 heterodimers that translocate to the nucleus and form an ISGF3 complex by associating on DNA with IRF9. The higher off-rate of STAT2–IRF9 compared with ISGF3 combined with a larger quantity of tyrosine-phosphorylated STAT1–STAT2 versus STAT2–RF9 complexes in IFN-treated cells most likely explains why a rapid exchange takes place after interferon treatment
