Structure and function of USP5: Insight into physiological and pathophysiological roles. (July 2020)

• Record Type: Journal Article
• Authors: Ning, Fengling; Xin, Hong; Liu, Junqiu; Lv, Chao; Xu, Xin; Wang, Mengling; Wang, Yinhang; Zhang, Weidong; Zhang, Xuemei
• Is Part Of: Pharmacological research. Volume 157(2020)
• Publication Date: 2020-07
• Subjects: Formononetin (CID 5280378) -- Gossypetin (CID 5280647) -- Mebendazole (CID 4030) -- PYR-41 (CID 5335621) -- Suramin (CID 5361) -- Vemurafenib (CID 42611257) -- Vialinin A (CID 11563133) -- WP1130 (CID 11222830); CRC colorectal cancer -- DUBs deubiquitinases -- EBF1 EBF transcription factor 1 -- EMT epithelial-mesenchymal transition -- GBM glioblastoma multiforme -- HCC hepatocellular carcinoma -- IFNs Type I interferons -- ISOT isopeptidase T -- JAMM JAB1/MPN/Mov34 metalloenzyme -- JNK Jun N-terminal kinase -- Met1 N-terminal methionine -- MJD Machado-Joseph disease protease -- MM multiple myeloma -- NICD Notch intracellular domain -- NSCLC non-small cell lung cancer -- OUT Otubain protease -- PDAC pancreatic ductal adenocarcinoma -- PTB polypyrimidine tract-binding protein -- PTBP1 polypyrimidine tract-binding protein 1 -- RBL-2H3 rat basophilic leukemia -- RIG-I retinoic acid-inducible gene-I -- SGs stress granules -- Smurf1 Smad ubiquitination regulatory factor 1 -- TNF-α Tumor necrosis factor alpha -- TUFM Tu translation elongation factor -- UCH ubiquitin C-terminal hydrolase -- USP ubiquitin-specific protease -- USP5 ubiquitin-specific proteinase 5 -- ZnF-UBP zinc finger ubiquitin-specific protease; Cancer -- Deubiquitinating enzyme -- DUB inhibitors -- Inflammation -- Neurological pain -- USP5; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.104557
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: 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 ubiquitin-specific 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.