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A review of deubiquitinases and thier roles in tumorigenesis and development

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FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2023.1204472

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deubiquitinase; deubiquitination; tumor treatment; deubiquitinase inhibitor; cancer

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Ubiquitin is a small protein that can be added onto target protein to induce degradation and modulate the activity and stability of the protein. Deubiquitinases (DUBs) are a class of enzymes that can remove ubiquitin from substrate proteins, providing positive regulation at the transcriptional level, post-translational modification, protein interaction, etc. The reversible and dynamic process of ubiquitination-deubiquitination plays a critical role in maintaining protein homeostasis and is essential for almost all biological processes.
Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs.

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