Interferon-stimulated gene 15 and ISGylation are upregulated in glioblastoma

Interferon stimulated gene 15 (ISG15) encodes a 15-kDa ubiquitin-like protein that acts as a posttranslational modifier of target proteins via ISGylation, a catalytic process similar to ubiquitination. Protein ISGylation is associated with the modulation of protein stability and protein-protein interactions. Furthermore, non-conjugated ISG15 (free ISG15) is secreted to act as a cytokine-like protein in some cellular contexts. The expression of ISG15 in some cancer types is dysregulated, but its expression status in glioblastoma, a malignant brain tumor highly aggressive and invasive, requires more studies. To explore the potential of ISG15 as a biomarker for glioblastoma, we first evaluated the ISG15 levels in glioblastoma cell lines and the effect of IFN-γ treatment on protein levels and localization of ISG15. In addition, we analyzed the ISG15 levels in glioblastoma samples compared to healthy brain tissue. Our results indicate that ISG15 levels are increased in glioblastoma and are upregulated in response to IFN-γ stimulus, suggesting that ISG15 and ISGylation may play a central role in glioblastoma progression. Thus, ISG15/ISGyaltion may be useful as biomarkers of this type of malignant brain tumors.