Figure 1

IFN-γ-inducible CIITA transcription from the type IV promoter is mediated by the Janus Kinase-1/Signal Transducers and Activators of Transcription-1 (JAK-1/STAT-1) signaling pathway. Binding of IFN-γ to the IFN-γ receptor (IFN-γ-R) results in activation of the kinases JAK-1 and JAK-2. These kinases subsequently phosphorylate the IFN-γ-R, which leads to a conformational change in the receptor that provides a docking site for monomers of the transcription factor STAT-1 that are localized in the cytoplasm. These STAT-1 monomers are phosphorylated by the JAKs, which leads to dimerization and translocation to the nucleus. STAT-1 activates transcription of a variety of genes, including the transacting factor interferon regulatory factor-1 (IRF-1), by binding to γ-activating sequences (GAS) within the promoters of the target genes. Phosphorylated STAT-1, IRF-1, and the ubiquitously expressed factors USF-1 and IRF-2 subsequently cooperate to activate CIITA transcription by binding to the GAS, E box and interferon responsive element (IRE), respectively, in the CIITA type IV promoter.