Ubiquitin-specific protease 20 in human disease: Emerging role and therapeutic implications

Abstract

Ubiquitination is one of the most important post-translational protein modifications; the linking of the 76-amino-acid polypeptide ubiquitin dictates protein fate. Deubiquitinating enzymes (DUBs) can specifically remove ubiquitin attached to substrate proteins, thereby stabilizing the protein and preventing its degradation through the proteasome. The balance between ubiquitination and deubiquitination plays a key role in maintaining protein function and in regulating cellular homeostasis. The development of drugs targeting DUBs has attracted the widespread attention of scientists and pharmaceutical companies. Ubiquitin-specific protease 20 (USP20) belongs to the ubiquitin-specific peptidase (USP) subfamily of DUBs and its important physiological role has been assessed in recent years. Previous studies on USP20 have focused on its activity in antiviral immunity and cancer. However, its role in metabolic disorders and neurological diseases has also been revealed. The physiological importance of USP20 in disease is being reported continuously, indicating its potential to be a valuable therapeutic target in the future. The small molecule inhibitor GSK2643943A has been shown to inhibit the deubiquitination activity of USP20. Herein, we discuss the structure, regulation, and emerging physiological roles of USP20 in disease, hoping to highlight their therapeutic implications for future studies.

Keywords: Emerging physiological role; Molecular regulation; Structure analysis; Therapeutic implications; USP20.