Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress

Jeon, Young Joo; Park, Jong Ho; Chung, Chin Ha

UBLs are small-size polypeptides whose three-dimensional structures are strikingly similar to that of ubiquitin, although the similarity in their amino acid sequences to ubiquitin sig-nificantly varies (Kerscher et al., 2006) . So far more than ten UBLs have been identified and they include ATG8, FAT10, HUB1, ISG15, NEDD8, SUMO(1-4), UFM1, and URM1 (Jentsch and Pyrowolakis, 2000) . Most UBLs are conjugated to specific target proteins by a three-enzyme cascade system (E1, E2, and E3) that resembles ubiquitination. Protein modifications by ubiquitin and UBLs are reversible processes that are catalyzed by isopeptidases, called deubiquitinating enzymes (DUBs) and UBL-specific proteases (ULPs), respectively. These reversible protein modification processes play important roles in the regulation of key cellular processes, including cell proliferation, cell differentiation, and apoptosis. Furthermore, deregulation of these modification systems results in a wide variety of human diseases, including cancer, neurodegenerative disorders, and immune diseases.