Affiliation:
1. College of Biotechnology, Misr University for Science and Technology, Giza, Egypt
2. Drug Design and Discovery
Laboratory, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Cairo,
Egypt, 12578 | Biomedical Sciences Program, University of Science and Technology, Zewail City of Science
and Technology, Cairo, Egypt, 12578
Abstract
:
As cancer continues to be one of the leading causes of death, various cancer treatments
are being developed from traditional surgery to the more recent emergence of target
therapy. However, therapy resistance is a restricting problem that needs to be overcome.
Henceforth, the field of research shifts to new plausible drug targets, among which is the
ubiquitin-proteasome system. This review is focused on the ubiquitin carboxyl-terminal hydrolase
(UCH) protease family, which are members of Deubiquitinating enzymes (DUBs),
specifically Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3). DUBs regulate a broad array
of regulatory processes, including cell-cycle progression, tissue development, and differentiation.
DUBs are classified into seven subfamilies, including ubiquitin-specific proteases
(USPs), JAB1/MPN/Mov34 metalloenzyme, ovarian tumor proteases (OTUs), Josephin and
JAB1/MPN+(MJP), MIU-containing novel DUB (MINDY), zinc finger-containing ubiquitin
peptidase 1 (ZUP1), and ubiquitin C-terminal hydrolases (UCHs). Having a significant role in
tumorigenesis, UCHL3 is thus emerging as a therapeutic target. Knowing its involvement in
cancer, it is important to understand the structure of UCHL3, its substrate specificity, and interaction
to pave the way for the development of potential inhibitors. This review covers several
directions of proteasome inhibitors drug discovery and small molecule inhibitors development.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
2 articles.
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