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SENP Proteases as Potential Targets for Cancer Therapy
SIMPLE SUMMARY: Post-translational modification—the biochemical addition of functional groups or proteins—occurs following protein biosynthesis and contributes to an increase in the functional diversity of the proteome. Post-translational modifications include SUMOylation—the covalent attachment of...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123143/ https://www.ncbi.nlm.nih.gov/pubmed/33923236 http://dx.doi.org/10.3390/cancers13092059 |
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author | Tokarz, Paulina Woźniak, Katarzyna |
author_facet | Tokarz, Paulina Woźniak, Katarzyna |
author_sort | Tokarz, Paulina |
collection | PubMed |
description | SIMPLE SUMMARY: Post-translational modification—the biochemical addition of functional groups or proteins—occurs following protein biosynthesis and contributes to an increase in the functional diversity of the proteome. Post-translational modifications include SUMOylation—the covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMOylation is a reversible modification, which is erased by SUMO-specific proteases (SENPs). Deregulation of SENPs leads to cellular dysfunction and is associated with various diseases, including cancer. The role of SENPs in cancer pathogenesis is expected, and thus these proteins are considered promising targets for drug design and development. In this review, we will discuss the role of SENPs, focusing on DNA repair and the cell cycle—cellular pathways malfunctioning in most cancer cells—and provide an update on advances in the development of SENP-oriented inhibitors. ABSTRACT: SUMOylation is a reversible post-translational modification (PTM) involving a covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMO-specific proteases (SENPs) are cysteine proteases with isopeptidase activity facilitating the de-conjugation of SUMO proteins and thus participating in maintaining the balance between the pools of SUMOylated and unSUMOylated proteins and in SUMO recycling. Several studies have reported that SENPs’ aberrant expression is associated with the development and progression of cancer. In this review, we will discuss the role of SENPs in the pathogenesis of cancer, focusing on DNA repair and the cell cycle—cellular pathways malfunctioning in most cancer cells. The plausible role of SENPs in carcinogenesis resulted in the design and development of their inhibitors, including synthetic protein-based, peptide-based, and small molecular weight inhibitors, as well as naturally occurring compounds. Computational methods including virtual screening have been implemented to identify a number of lead structures in recent years. Some inhibitors suppressed the proliferation of prostate cancer cells in vitro and in vivo, confirming that SENPs are suitable targets for anti-cancer treatment. Further advances in the development of SENP-oriented inhibitors are anticipated toward SENP isoform-specific molecules with therapeutic potential. |
format | Online Article Text |
id | pubmed-8123143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81231432021-05-16 SENP Proteases as Potential Targets for Cancer Therapy Tokarz, Paulina Woźniak, Katarzyna Cancers (Basel) Review SIMPLE SUMMARY: Post-translational modification—the biochemical addition of functional groups or proteins—occurs following protein biosynthesis and contributes to an increase in the functional diversity of the proteome. Post-translational modifications include SUMOylation—the covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMOylation is a reversible modification, which is erased by SUMO-specific proteases (SENPs). Deregulation of SENPs leads to cellular dysfunction and is associated with various diseases, including cancer. The role of SENPs in cancer pathogenesis is expected, and thus these proteins are considered promising targets for drug design and development. In this review, we will discuss the role of SENPs, focusing on DNA repair and the cell cycle—cellular pathways malfunctioning in most cancer cells—and provide an update on advances in the development of SENP-oriented inhibitors. ABSTRACT: SUMOylation is a reversible post-translational modification (PTM) involving a covalent attachment of small ubiquitin-related modifier (SUMO) proteins to substrate proteins. SUMO-specific proteases (SENPs) are cysteine proteases with isopeptidase activity facilitating the de-conjugation of SUMO proteins and thus participating in maintaining the balance between the pools of SUMOylated and unSUMOylated proteins and in SUMO recycling. Several studies have reported that SENPs’ aberrant expression is associated with the development and progression of cancer. In this review, we will discuss the role of SENPs in the pathogenesis of cancer, focusing on DNA repair and the cell cycle—cellular pathways malfunctioning in most cancer cells. The plausible role of SENPs in carcinogenesis resulted in the design and development of their inhibitors, including synthetic protein-based, peptide-based, and small molecular weight inhibitors, as well as naturally occurring compounds. Computational methods including virtual screening have been implemented to identify a number of lead structures in recent years. Some inhibitors suppressed the proliferation of prostate cancer cells in vitro and in vivo, confirming that SENPs are suitable targets for anti-cancer treatment. Further advances in the development of SENP-oriented inhibitors are anticipated toward SENP isoform-specific molecules with therapeutic potential. MDPI 2021-04-24 /pmc/articles/PMC8123143/ /pubmed/33923236 http://dx.doi.org/10.3390/cancers13092059 Text en © 2021 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 Tokarz, Paulina Woźniak, Katarzyna SENP Proteases as Potential Targets for Cancer Therapy |
title | SENP Proteases as Potential Targets for Cancer Therapy |
title_full | SENP Proteases as Potential Targets for Cancer Therapy |
title_fullStr | SENP Proteases as Potential Targets for Cancer Therapy |
title_full_unstemmed | SENP Proteases as Potential Targets for Cancer Therapy |
title_short | SENP Proteases as Potential Targets for Cancer Therapy |
title_sort | senp proteases as potential targets for cancer therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123143/ https://www.ncbi.nlm.nih.gov/pubmed/33923236 http://dx.doi.org/10.3390/cancers13092059 |
work_keys_str_mv | AT tokarzpaulina senpproteasesaspotentialtargetsforcancertherapy AT wozniakkatarzyna senpproteasesaspotentialtargetsforcancertherapy |