Journal
GENES
Volume 13, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/genes13050831
Keywords
deubiquitinating enzymes (DUBs); USP10; tumorigenesis; inhibitors; therapeutic strategy
Categories
Funding
- Henan National Science Fund for Excellent Young Scholars [212300410067]
- National Natural Science Foundation of China [82074360]
- Doctoral Foundation of Xinxiang Medical University [XYBSKYZZ202001]
- Young Tai shan Scholars Program of Shandong Province [tsqn201909200]
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This review summarizes the dual role of deubiquitinating enzyme USP10 in human cancers as well as its downstream substrates and upstream regulators. Additionally, it provides an overview of multiple pharmacological USP10 inhibitors and proposes the development of specific and efficient USP10 inhibitors as a promising therapeutic strategy for cancer treatment.
Deubiquitination is a major form of post-translational protein modification involved in the regulation of protein homeostasis and various cellular processes. Deubiquitinating enzymes (DUBs), comprising about five subfamily members, are key players in deubiquitination. USP10 is a USP-family DUB featuring the classic USP domain, which performs deubiquitination. Emerging evidence has demonstrated that USP10 is a double-edged sword in human cancers. However, the precise molecular mechanisms underlying its different effects in tumorigenesis remain elusive. A possible reason is dependence on the cell context. In this review, we summarize the downstream substrates and upstream regulators of USP10 as well as its dual role as an oncogene and tumor suppressor in various human cancers. Furthermore, we summarize multiple pharmacological USP10 inhibitors, including small-molecule inhibitors, such as spautin-1, and traditional Chinese medicines. Taken together, the development of specific and efficient USP10 inhibitors based on USP10's oncogenic role and for different cancer types could be a promising therapeutic strategy.
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