Title: The regulatory role of free ISG15
Interferons(IFNs) are a group of cytokinesinduced by viral infection. IFN production leads to a series of protein conformationalrearrangements and interactions as well as production of specific proteins. InterferonStimulated Gene 15 (ISG15) is one protein which is highly induced in responseto IFN production. ISG15 is an abundant ubiquitin-like post-translationmodification that, similar to Ubiquitin (Ub), marks hundreds of cellularproteins following viral or bacterial infections. ISG15’s targets include bothviral proteins and cellular proteins spanning an array of cellular compartmentsand metabolic pathways. As opposed to Ub, that is consumed almost completelyand is hardly present in its free form, ISG15 can be found in the cell in twoforms: free ISG15 and as a part of a chain. It is known that free ISG15 can besecreted and act as a cytokine like protein, inducing the IFN pathway of theneighboring cells. In our research, we found a different regulatory role of thefree ISG15. By investigating its binding partners, we found that ISG15 can bindthe transcription factor that enables its production in the first place, thusacting as autoregulator of its own level and effect the innate immune responseof the cell.