Page 91 - GPD-1-2

Gene & Protein in Disease

REVIEW ARTICLE
Recent insights into USP7: Construct,

pathophysiology, and inhibitors

1
Yuanming He , Yueya Zhong , Yiqian Wang , and Xinliang Mao *
1
1
2
1 Guangzhou and Guangdong Key Laboratory of Protein Modification and Degradation, School of
Basic Medical Sciences and State Key Laboratory of Respiratory Diseases, Guangzhou Medical
University, Panyu District, Guangzhou, 511436, China
2 School of Biological Sciences, Guangzhou Medical University, Panyu District, Guangzhou, 511436,
China
Abstract

The ubiquitin-proteasome pathway (UPP) is essential for proteostasis and cellular
homeostasis. Most of the human proteins are degraded through the UPP in which
proteins should be tagged with a specific polyubiquitin chain in a sequential cascade
of E1 ubiquitin (Ub)-activating enzymes, namely, E2 Ub-conjugating enzymes and E3
Ub ligases. Meanwhile, the ubiquitination process can be reversed by deubiquitinating
enzymes (DUBs), which protect the target proteins from ubiquitination, and so far,
around 100 DUBs have been reported to present in human cells. Ubiquitin-specific
protease 7 (USP7) is a member of the DUBs family, which has been reported to
play crucial role in the development of human tumors and diseases; however, the
molecular mechanisms of disease and malignant tumor progression mediated by
USP7 has not been fully elucidated. In addition, the therapeutic potential of USP7 in
cancer treatment remains to be further explored. Therefore, this review begins with a
review of the structure and function of USP7, and then focuses on the development
of USP7 inhibitors and their potential applications in various human diseases.

*Corresponding author:
Xinliang Mao Keywords: Degradation; Ubiquitin-proteasome pathway; Deubiquitinating enzymes;
(xinliangmao@gzhmu.edu.cn)
Ubiquitin specific protease 7; Molecule inhibitors
Citation: He Y, Zhong Y, Wang Y,
et al., 2022, Recent insights into
USP7: Construct, pathophysiology,
and inhibitors. Gene Protein Dis,
1(2):118. 1. Introduction
https://doi.org/10.36922/gpd.v1i2.118
Ubiquitination is an essential and important post-translational modification process for
Received: May 30, 2022
Accepted: July 18, 2022 most of the proteins, through which the proteins are covalently tagged with ubiquitin
Published Online: August 15, 2022 (Ub) molecules. Ub molecule, which is composed of 76 amino acids, is widely expressed,
[1]
Copyright: © 2022 Author(s). and the structure of the molecules is highly conserved across different species . At the
This is an Open Access article consumption of ATP, Ub molecules are covalently conjugated to a certain lysine residue
distributed under the terms of the
Creative Commons Attribution of the target protein, which is further catalyzed by the E1 Ub-activating enzymes (for
License, permitting distribution, activation), E2 Ub-conjugating enzymes (for conjugation), and E3 Ub ligases (for
and reproduction in any medium, [2]
provided the original work is ligation) . It has been reported that there are around 2 Ub-activating enzymes (E1s),
properly cited. at least 38 Ub-conjugating enzymes (E2s), and more than 600 Ub ligases (E3s) in
Publisher’s Note: AccScience human, and the specific combinations of these enzymes determine the specificity of
Publishing remains neutral with the protein ubiquitination process. Interestingly, Ub molecules contain seven lysine
regard to jurisdictional claims in
published maps and institutional residues, namely K6, K11, K27, K29, K33, K48, and K63, which could be conjugated
affiliations. to other Ub molecules, providing diversity, and specificity for the ubiquitination

Volume 1 Issue 2 (2022) 1 https://doi.org/10.36922/gpd.v1i2.118