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Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches
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Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches
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Journal Article
Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches
2024
Overview
Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin–proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Animals
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Biomedical and Life Sciences
/ Cancer
/ Deubiquitinating Enzymes - metabolism
/ Humans
/ Ligases
/ Oncology
/ Post-translational modification
/ Proteasome Endopeptidase Complex - metabolism
/ Protein Processing, Post-Translational
/ Review
