Journal
PHARMACOLOGICAL RESEARCH
Volume 157, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2019.104557
Keywords
Cancer; Deubiquitinating enzyme; DUB inhibitors; Inflammation; Neurological pain; USP5
Categories
Funding
- National Natural Science Foundation of China [81973385, 81773801]
- Natural Science Foundation of Jiangsu Province [BK20171231]
- Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology), Zhejiang Chinese Medical University [ZYAOX2018002]
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Deubiquitinase (DUB)-mediated cleavage of ubiquitin chains from substrate proteins plays a crucial role in various cellular processes, such as DNA repair and protein stabilization and localization. DUBs can be classified into five families based on their sequence and structural homology, and the majority belong to the ubiquitinspecific proteinase (USP) family. As one of the USPs, ubiquitin-specific proteinase 5 (USP5) is unique in that it can specifically recognize unanchored (not conjugated to target proteins) polyubiquitin and is essential for maintaining homeostasis of the monoubiquitin pool. USP5 has also been implicated in a wide variety of cellular events. In the present review, we focus on USP5 and provide a comprehensive overview of the current knowledge regarding its structure, physiological roles in multiple cellular events, and pathophysiological roles in relevant diseases, especially cancer. Signaling pathways and emerging pharmacological profiles of USP5 are also introduced, which fully embody the therapeutic potential of USP5 for human diseases ranging from cancer to neurological diseases.
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