Non-conventional signal transduction by type I interferons:: The NF-κB pathway

Type I interferons (IFNs) regulate diverse cellular functions by modulating the expression of IFN-stimulated genes (ISGs) through the activation of the well established signal transduction pathway of the Janus Kinase (JAK) and signal transducers and activators of transcription (STAT) proteins. Although the JAK-STAT signal transduction pathway is critical in mediating IFN's antiviral and antiproliferative activities, other signaling pathways are activated by IFNs and regulate cellular response to IFN. The NF-kappa B transcription factor regulates the expression of genes involved in cell survival and immune responses. We have identified a novel IFN mediated signal pathway that leads to NF-kappa B activation and demonstrate that a subset of ISGs that play key roles in cellular response to IFN is regulated by NF-kappa B. This review focuses on the IFN-induced NF-kappa B activation pathway and the role of NF-kappa B in ISG expression, antiviral activity and apoptosis, and the therapeutic application of IFN in cancer and infectious disease.