Journal
PHARMACEUTICALS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ph14090848
Keywords
cancer; ubiquitin; deubiquitination; deubiquitinating enzymes (DUBs); ubiquitin-specific proteases (USPs); USP inhibitors
Categories
Funding
- European Regional Development Fund under the project The Porto Comprehensive Cancer Center [NORTE-01-0145-FEDER-072678]
- Programa Operacional Regional do Norte
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Ubiquitination and deubiquitinating enzymes play crucial roles in cellular regulation, especially in the development of cancer. USPs, as the largest family of DUBs, are involved in various cellular functions and have been studied as novel targets for cancer therapy.
Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.
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