DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases
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 mark ubiquitinated proteins for protea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/10/1503 |
| _version_ | 1797574487770660864 |
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| author | Thomas Klonisch Susan E. Logue Sabine Hombach-Klonisch Jerry Vriend |
| author_facet | Thomas Klonisch Susan E. Logue Sabine Hombach-Klonisch Jerry Vriend |
| author_sort | Thomas Klonisch |
| collection | DOAJ |
| description | 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 mark 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. |
| first_indexed | 2024-03-10T21:24:10Z |
| format | Article |
| id | doaj.art-14a69a1ffa9b4fedabec529787c8d576 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T21:24:10Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-14a69a1ffa9b4fedabec529787c8d5762023-11-19T15:50:10ZengMDPI AGBiomolecules2218-273X2023-10-011310150310.3390/biom13101503DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of DeubiquitinasesThomas Klonisch0Susan E. Logue1Sabine Hombach-Klonisch2Jerry Vriend3Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaDepartment of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaDepartment of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaDepartment of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, CanadaThe 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 mark 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.https://www.mdpi.com/2218-273X/13/10/1503brain tumorgliomaneuronal system tumordeubiquitinase (DUB)endoplasmic reticulum associated degradation (ERAD)immune response |
| spellingShingle | Thomas Klonisch Susan E. Logue Sabine Hombach-Klonisch Jerry Vriend DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases Biomolecules brain tumor glioma neuronal system tumor deubiquitinase (DUB) endoplasmic reticulum associated degradation (ERAD) immune response |
| title | DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases |
| title_full | DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases |
| title_fullStr | DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases |
| title_full_unstemmed | DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases |
| title_short | DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases |
| title_sort | dubing primary tumors of the central nervous system regulatory roles of deubiquitinases |
| topic | brain tumor glioma neuronal system tumor deubiquitinase (DUB) endoplasmic reticulum associated degradation (ERAD) immune response |
| url | https://www.mdpi.com/2218-273X/13/10/1503 |
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