CCAAT/Enhancer Binding Proteins and Interferon Signaling Pathways

Interferons (IFNs) regulate a number of host responses, including innate and adaptive immunity against viruses, microbes, and neoplastic cells. These responses are dependent on the expression of IFN-stimulated genes (ISGs). Given the diversities in these responses and their kinetics, it is conceivable that a number of different factors are required for controlling them. Here, we describe one such pathway wherein transcription factor CAAAT/enhancer binding protein-beta (C/EBP-beta) is controlled via IFN-gamma-induced MAPK signaling pathways. At least two IFN-gamma-induced MAPK signals converge on to C/EBP-beta for inducing transcription. One of these, driven by extracellular signal-regulated kinases (ERKs), phosphorylates the C/EBP-beta protein in its regulatory domain. The second, driven by the mixed-lineage kinases (MLKs), induces a dephosphorylation leading to the recruitment of transcriptional coactivators.