UBE1L/UBA7 Antibody #69023

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 (1). Expression of ISG15 is stimulated by cellular exposure to type 1 interferons α and β, in addition to infection with viruses such as influenza B (2,3). After exposure to type I interferons, both lymphocytes and monocytes, in addition to some fibroblasts and epithelial cells, release ISG15 into culture medium (1,4). ISG15 has been shown to function as a cytokine, stimulating interferon γ secretion by monocytes and macrophages, proliferation of natural killer cells, and chemotactic responses in neutrophils (4,5). 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 (6,7). ISG15 is removed from proteins by the ubiquitin processing protease Ubp43 (8). ISG15-protein conjugation (ISGylation) is induced by type 1 interferons, and target proteins include the serine protease inhibitor Serpin 2A, PLCγ1, ERK1/2, Jak1 and Stat1 (9,10). Unlike ubiquitination, ISGylation does not target proteins for degradation, rather ISGylation increases Jak1 and Stat1 activity, enhancing the cellular response to interferons (11).
Ubiquitin-activating enzyme E1-like protein/Ubiquitin-activating enzyme 7 (UBE1L/UBA7) is the activating enzyme for ISG15. Research studies have suggested that loss of UBE1L/UBA7 expression contributes to the development of lung cancer due to compromised inhibition of cyclin D1 expression (12-15). UBE1L/UBA7 has also been implicated in the pathogenesis acute promyelocytic leukemia through a mechanism in which UBE1L/UBA7 drives ISG15ylation of the oncogenic PML-RARα fusion protein to promote its degradation (16,17).