Klonisch, T.; Logue, S.E.; Hombach-Klonisch, S.; Vriend, J. DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases. Biomolecules2023, 13, 1503.
Klonisch, T.; Logue, S.E.; Hombach-Klonisch, S.; Vriend, J. DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases. Biomolecules 2023, 13, 1503.
Klonisch, T.; Logue, S.E.; Hombach-Klonisch, S.; Vriend, J. DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases. Biomolecules2023, 13, 1503.
Klonisch, T.; Logue, S.E.; Hombach-Klonisch, S.; Vriend, J. DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases. Biomolecules 2023, 13, 1503.
Abstract
The ubiquitin proteasome system (UPS) utilizes an orchestrated enzymatic cascade of E1, E2, and E3 ligases to add single or multiple ubiquitin-like molecules as post-translational modification (PTM) to proteins. Ubiquitination can alter protein functions and/ or marks ubiquitinated proteins for proteasomal degradation but deubiquitinases (DUBs) can reverse protein ubiquitination. While the importance of DUBs as regulatory factors in the UPS is undisputed, many questions remain on DUB selectivity for protein targeting, their mechanism of action, and the impact of DUBs on the regulation of diverse biological processes. Furthermore, little is known about the expression and role of DUBs in tumors of the human central nervous system (CNS). In this comprehensive review, we have used publicly available transcriptional datasets to determine the gene expression profiles of 99 deubiquitinases (DUBs) from five major DUB families in seven primary pediatric and adult CNS tumor entities. Our analysis identified selected DUBs as potential new functional players and biomarkers with prognostic value in specific subtypes of primary CNS tumors. Collectively, our analysis highlights an emerging role for DUBs in regulating CNS tumor cell biology and offers a rationale for future therapeutic targeting of DUBs in CNS tumors.
Keywords
brain tumor; glioma; neuronal system tumor; deubiquitinase (DUB); Endoplasmic Reticulum Associated Degradation (ERAD); immune response; therapeutic target; DNA repair
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
