Schematic of IFNG signaling through the JAK/STAT1 pathway. Binding of IFNG to its receptor results in activation of the JAKs, which phosphorylate cytoplasmic monomers of STAT1. Phosphorylated STAT1 dimerizes, translocates to the nucleus, and activates transcription from gene promoters containing GAS (primary responses), such as IRF1. In the secondary responses, IRF1 activates transcription of IRF2, CDKN1A, caspases, and the MHC class Ia genes by binding IFN response elements (IRE), whereas STAT1 and IRF1 cooperate to transactivate expression of other genes, such as guanylate binding protein (GBP), PSMB8, PSMB9, and CIITA. P, phosphorylated.