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The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer
Until recently, Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that our knowledge of this class of E3-ubiquitin ligases is st...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340142/ https://www.ncbi.nlm.nih.gov/pubmed/37443713 http://dx.doi.org/10.3390/cells12131680 |
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author | Scalia, Pierluigi Williams, Stephen J. Suma, Antonio Carnevale, Vincenzo |
author_facet | Scalia, Pierluigi Williams, Stephen J. Suma, Antonio Carnevale, Vincenzo |
author_sort | Scalia, Pierluigi |
collection | PubMed |
description | Until recently, Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that our knowledge of this class of E3-ubiquitin ligases is still at an early stage, our understanding of their role in oncogenesis is beginning to unfold. In fact, recently published studies allow us to define specific biological scenarios and further consolidate evidence-based working hypotheses. According to the current evidence, all DTX family members are involved in the regulation of Notch signaling, suggesting a phylogenetically conserved role in the regulation of this pathway. Indeed, additional evidence reveals a wider involvement of these proteins in other signaling complexes and cancer-promoting mechanisms beyond NOTCH signaling. DTX3, in particular, had been known to express two isoform variants (DTX3a and DTX3b). The recent identification and cloning of a third isoform variant in cancer (DTX3c), and its specific involvement in EphB4 degradation in cancer cells, sheds further light on this group of proteins and their specific role in cancer. Herein, we review the cumulative knowledge of this family of E3 Ubiquitin ligases with a specific focus on the potential oncogenic role of DTX isoforms in light of the rapidly expanding findings regarding this protein family’s cellular targets and regulated signaling pathways. Furthermore, using a comparative and bioinformatic approach, we here disclose a new putative motif of a member of this family which may help in understanding the biological and contextual differences between the members of these proteins. |
format | Online Article Text |
id | pubmed-10340142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103401422023-07-14 The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer Scalia, Pierluigi Williams, Stephen J. Suma, Antonio Carnevale, Vincenzo Cells Review Until recently, Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that our knowledge of this class of E3-ubiquitin ligases is still at an early stage, our understanding of their role in oncogenesis is beginning to unfold. In fact, recently published studies allow us to define specific biological scenarios and further consolidate evidence-based working hypotheses. According to the current evidence, all DTX family members are involved in the regulation of Notch signaling, suggesting a phylogenetically conserved role in the regulation of this pathway. Indeed, additional evidence reveals a wider involvement of these proteins in other signaling complexes and cancer-promoting mechanisms beyond NOTCH signaling. DTX3, in particular, had been known to express two isoform variants (DTX3a and DTX3b). The recent identification and cloning of a third isoform variant in cancer (DTX3c), and its specific involvement in EphB4 degradation in cancer cells, sheds further light on this group of proteins and their specific role in cancer. Herein, we review the cumulative knowledge of this family of E3 Ubiquitin ligases with a specific focus on the potential oncogenic role of DTX isoforms in light of the rapidly expanding findings regarding this protein family’s cellular targets and regulated signaling pathways. Furthermore, using a comparative and bioinformatic approach, we here disclose a new putative motif of a member of this family which may help in understanding the biological and contextual differences between the members of these proteins. MDPI 2023-06-21 /pmc/articles/PMC10340142/ /pubmed/37443713 http://dx.doi.org/10.3390/cells12131680 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Scalia, Pierluigi Williams, Stephen J. Suma, Antonio Carnevale, Vincenzo The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title | The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title_full | The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title_fullStr | The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title_full_unstemmed | The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title_short | The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer |
title_sort | dtx protein family: an emerging set of e3 ubiquitin ligases in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340142/ https://www.ncbi.nlm.nih.gov/pubmed/37443713 http://dx.doi.org/10.3390/cells12131680 |
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