생화학분자생물학회

	Young Joo Jeon( yjjeon@cnu.ac.kr )
	2020-present	Associate Professor, Chungnam National University College of Medicine, South Korea
	2015-2020	Assistant Professor, Chungnam National University College of Medicine, South Korea
	2012-2015	Postdoctoral Associate, Sanford Burnham Prebys Medical Discovery Institute, USA
	2010-2012	BK21 Assistant Professor, Brain Korea 21, Seoul National University, South Korea
	2006-2010	Research Assistant Professor, School of Biological Sciences, Seoul National University, South Korea
	2000-2006	Ph.D., School of Biological Sciences, Seoul National University, South Korea
	1998-2000	M.S., Department of Molecular Biology, Seoul National University, South Korea

The diverse repertoire of ISG15: more intricate than initially thought

ISG15, the product of interferon (IFN)-stimulated gene 15, is the first identified ubiquitin-like protein (UBL), which plays multifaceted roles not only as a free intracellular or extracellular molecule but also as a post-translational modifier in the process of ISG15 conjugation (ISGylation). ISG15 has only been identified in vertebrates, indicating that the functions of ISG15 and its conjugation are restricted to higher eukaryotes and have evolved with IFN signaling. Despite the highlighted complexity of ISG15 and ISGylation, it has been suggested that ISG15 and ISGylation profoundly impact a variety of cellular processes, including protein translation, autophagy, exosome secretion, cytokine secretion, cytoskeleton dynamics, DNA damage response, telomere shortening, and immune modulation, which emphasizes the necessity of reassessing ISG15 and ISGylation. However, the underlying mechanisms and molecular consequences of ISG15 and ISGylation remain poorly defined, largely due to a lack of knowledge on the ISG15 target repertoire. In this review, we provide a comprehensive overview of the mechanistic understanding and molecular consequences of ISG15 and ISGylation. We also highlight new insights into the roles of ISG15 and ISGylation not only in physiology but also in the pathogenesis of various human diseases, especially in cancer, which could contribute to therapeutic intervention in human diseases.

Exp Mol Med. 2022 Nov;54(11):1779-1792. doi: 10.1038/s12276-022-00872-3.
https://pubmed.ncbi.nlm.nih.gov/36319753/