Interferon (IFN)-I and IFN-II both induce IFN-stimulated gene (ISG) expression through
Janus kinase (JAK)-dependent phosphorylation of signal transducer and activator of transcription
(STAT) 1 and STAT2. STAT1 homodimers, known as γ-activated factor (GAF),
activate transcription in response to all types of IFNs by direct binding to IFN-II activation
site (γ-activated sequence)-containing genes. Association of interferon regulatory factor
(IRF) 9 with STAT1–STAT2 heterodimers [known as interferon-stimulated gene factor 3
(ISGF3)] or with STAT2 homodimers (STAT2/IRF9) in response to IFN-I, redirects these
complexes to a distinct group of target genes harboring the interferon-stimulated response
element (ISRE). Similarly, IRF1 regulates expression of ISGs in response to IFN-I and IFN-II
by directly binding the ISRE or IRF-responsive element. In addition, evidence is accumulating
for an IFN-independent and -dependent role of unphosphorylated STAT1 and
STAT2, with or without IRF9, and IRF1 in basal as well as long-term ISG expression. This
review provides insight into the existence of an intracellular amplifier circuit regulating ISG
expression and controlling long-term cellular responsiveness to IFN-I and IFN-II. The exact
timely steps that take place during IFN-activated feedback regulation and the control of
ISG transcription and long-term cellular responsiveness to IFN-I and IFN-II is currently
not clear. Based on existing literature and our novel data, we predict the existence of a
multifaceted intracellular amplifier circuit that depends on unphosphorylated and phosphorylated
ISGF3 and GAF complexes and IRF1. In a combinatorial and timely fashion,
these complexes mediate prolonged ISG expression and control cellular responsiveness
to IFN-I and IFN-II. This proposed intracellular amplifier circuit also provides a molecular
explanation for the existing overlap between IFN-I and IFN-II activated ISG expression.
这是一篇关于IFN-I的好文献，了解信号通路。
