Emerging Roles of USP18: From Biology to Pathophysiology

被引:58
作者
Kang, Ji An [1 ,2 ]
Jeon, Young Joo [1 ,2 ]
机构
[1] Chungnam Natl Univ, Dept Biochem, Coll Med, Daejeon 35015, South Korea
[2] Chungnam Natl Univ, Dept Med Sci, Coll Med, Daejeon 35015, South Korea
基金
新加坡国家研究基金会;
关键词
USP18; ubiquitin; ISG15; deubiquitinases; post-translational modifications; interferon signaling; UBIQUITIN-SPECIFIC PROTEASE; HEPATITIS-C VIRUS; ENHANCES ISG15 CONJUGATION; NF-KAPPA-B; I INTERFERON; UBP43; USP18; DEUBIQUITINASE USP18; IFN-ALPHA; EXPRESSION; CELLS;
D O I
10.3390/ijms21186825
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Eukaryotic proteomes are enormously sophisticated through versatile post-translational modifications (PTMs) of proteins. A large variety of code generated via PTMs of proteins by ubiquitin (ubiquitination) and ubiquitin-like proteins (Ubls), such as interferon (IFN)-stimulated gene 15 (ISG15), small ubiquitin-related modifier (SUMO) and neural precursor cell expressed, developmentally downregulated 8 (NEDD8), not only provides distinct signals but also orchestrates a plethora of biological processes, thereby underscoring the necessity for sophisticated and fine-tuned mechanisms of code regulation. Deubiquitinases (DUBs) play a pivotal role in the disassembly of the complex code and removal of the signal. Ubiquitin-specific protease 18 (USP18), originally referred to as UBP43, is a major DUB that reverses the PTM of target proteins by ISG15 (ISGylation). Intriguingly, USP18 is a multifaceted protein that not only removes ISG15 or ubiquitin from conjugated proteins in a deconjugating activity-dependent manner but also acts as a negative modulator of type I IFN signaling, irrespective of its catalytic activity. The function of USP18 has become gradually clear, but not yet been completely addressed. In this review, we summarize recent advances in our understanding of the multifaceted roles of USP18. We also highlight new insights into how USP18 is implicated not only in physiology but also in pathogenesis of various human diseases, involving infectious diseases, neurological disorders, and cancers. Eventually, we integrate a discussion of the potential of therapeutic interventions for targeting USP18 for disease treatment.
引用
收藏
页码:1 / 18
页数:18
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