Open Access

REVIEW

Ubiquitin Specific Protease 2: Structure, Isoforms, Cellular Function, Related Diseases and Its Inhibitors

by Hao Luo^1,#,*, Yanjie Ji^2,#, Xinrong Gao¹, Xinying Liu¹, Yunzhao Wu³, Yingli Wu^3,*

1 School of Basic Medicine, Weifang Medical University, Weifang, 261053, China
2 Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
3 Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

* Corresponding Authors: Hao Luo. Email: ; Yingli Wu. Email:
# Hao Luo and Yanjie Ji contributed equally to this work

Oncologie 2022, 24(1), 85-99. https://doi.org/10.32604/oncologie.2022.021705

Received 30 January 2022; Accepted 03 March 2022; Issue published 31 March 2022

Abstract

The ubiquitin-proteasome system (UPS) is an important pathway for cellular protein degradation. The components of this pathway, including the proteasome, ubiquitinase, and deubiquitinase, are highly specialized and strictly regulated. The ubiquitin-specific protease 2 (USP2) belongs to the ubiquitin-specific proteases, a subgroup of deubiquitinating enzymes. USP2 plays essential roles in regulating cell survival, cell cycle, circadian rhythm, cell metabolism, inflammatory response, antiviral response, and metastasis by interacting with certain proteins such as Cyclin D1, PER1, CRY1, HDM2/p53, FASN, LDLR, TRAF6, TBK1, and TGFBR1-TGFBR2 complex. Elevation of USP2 has been observed in a variety of cancers, including glioma, testicular cancer, breast cancer, prostate cancer, and some inflammatory diseases. Moreover, USP2 also plays an important role in many non-neoplastic diseases. At present, there is no officially approved USP2 inhibitor in clinic. A few existing inhibitors targeting USP2 have shown certain effects in the treatment of colorectal cancer, but their mechanism of action and binding site information are not clear. Moreover, the efficacy and selection specificity need to be further optimized. The catalytic centers of USP family are relatively conserved, so the design of compounds targeting allosteric site is expected to improve the specificity and inhibitory activity. In this review, we summarize the latest advances of USP2 in its cellular function, related diseases, and small-molecule inhibitors targeting USP2.

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