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Description
Interferon-stimulated 15 kDa protein (ISG15), also known as ubiquitin cross-reactive protein (UCRP), is a member of the ubiquitin-like protein family and functions in various biological pathways from pregnancy to innate immune responses . Expression of ISG15 is stimulated by cellular exposure to type 1 interferons alpha and beta, in addition to infection with viruses such as influenza B . After exposure to type I interferons, both lymphocytes and monocytes, in addition to some fibroblasts and epithelial cells, release ISG15 into culture medium . ISG15 has been shown to function as a cytokine, stimulating interferon gamma secretion by monocytes and macrophages, proliferation of natural killer cells, and chemotactic responses in neutrophils . ISG15 has also been shown to function intracellularly, being covalently conjugated to other proteins by E1 (Ube1L), E2 (UbcH8) and E3 ligases via a multi-step process analogous to ubiquitination . ISG15 is removed from proteins by the ubiquitin processing protease Ubp43 . ISG15-protein conjugation (ISGylation) is induced by type 1 interferons, and target proteins include the serine protease inhibitor Serpin 2A, PLCgamma1, ERK1/2, Jak1 and Stat1 . Unlike ubiquitination, ISGylation does not target proteins for degradation, rather ISGylation increases Jak1 and Stat1 activity, enhancing the cellular response to interferons . Synonyms: ISG15,G1P2,IFI15,UCRP ,