Human interferon-stimulated gene 15 (ISG15) is a 15-kDa ubiquitin-like protein that
can be detected as either free ISG15 or covalently associated with its target proteins through a process
termed ISGylation. Interestingly, extracellular free ISG15 has been proposed as a cytokinelike
protein, whereas ISGylation is a posttranslational modification. ISG15 is a small protein with
implications in some biological processes and pathologies that include cancer. This review highlights
the findings of both free ISG15 and protein ISGylation involved in several molecular pathways,
emerging as central elements in some cancer types.
Keywords: Free ISG15, conjugated ISG15, ISGylation system, cancer, proteins, molecular pathways.
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