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

by Selleckchem | Nov 22 2023

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.

Comments:

Ubiquitination and deubiquitination processes are crucial for maintaining cellular homeostasis and regulating various biological pathways. Ubiquitination, the attachment of ubiquitin molecules to substrate proteins, marks them for degradation by the proteasome or lysosomes. On the other hand, deubiquitinating enzymes (DUBs) like Ubiquitin-specific protease 20 (USP20) can remove ubiquitin from substrate proteins, stabilizing them and preventing degradation. The balance between ubiquitination and deubiquitination is essential for proper cellular functioning.

USP20, belonging to the ubiquitin-specific peptidase (USP) subfamily of DUBs, has gained significant attention from the scientific community. Studies have shown that USP20 plays a critical role in various physiological processes and diseases, extending beyond its previously known functions in antiviral immunity and cancer. Emerging research has uncovered its involvement in metabolic disorders and neurological diseases, broadening its significance as a potential therapeutic target.

One notable aspect of this research is the development of small molecule inhibitors such as GSK2643943A, which specifically target the deubiquitination activity of USP20. These inhibitors have shown promise in preclinical studies, raising hopes for potential therapeutic interventions in diseases where dysregulation of USP20 activity is implicated.

Understanding the structure and regulation of USP20 is essential for designing targeted therapies. Researchers are delving into the molecular intricacies of USP20 to identify potential drug targets and develop novel therapeutic strategies. By elucidating the physiological roles of USP20 in various diseases, scientists aim to pave the way for future therapeutic advancements.

Continued research on USP20 and its associated inhibitors holds significant promise in the field of drug discovery and may lead to the development of innovative treatments for a wide range of diseases, ultimately improving the quality of life for affected individuals.