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The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer
Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of ca...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979541/ https://www.ncbi.nlm.nih.gov/pubmed/33627786 http://dx.doi.org/10.1038/s41388-021-01679-8 |
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author | Morgan, Ethan L. Patterson, Molly R. Barba-Moreno, Diego Scarth, James A. Wilson, Adam Macdonald, Andrew |
author_facet | Morgan, Ethan L. Patterson, Molly R. Barba-Moreno, Diego Scarth, James A. Wilson, Adam Macdonald, Andrew |
author_sort | Morgan, Ethan L. |
collection | PubMed |
description | Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in ~15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic BCL-2 family. Furthermore, reduced Mcl-1 expression partially contributed to the observed proliferative defect in USP13 depleted cells. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers. |
format | Online Article Text |
id | pubmed-7979541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79795412021-04-12 The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer Morgan, Ethan L. Patterson, Molly R. Barba-Moreno, Diego Scarth, James A. Wilson, Adam Macdonald, Andrew Oncogene Article Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in ~15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic BCL-2 family. Furthermore, reduced Mcl-1 expression partially contributed to the observed proliferative defect in USP13 depleted cells. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers. Nature Publishing Group UK 2021-02-24 2021 /pmc/articles/PMC7979541/ /pubmed/33627786 http://dx.doi.org/10.1038/s41388-021-01679-8 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Morgan, Ethan L. Patterson, Molly R. Barba-Moreno, Diego Scarth, James A. Wilson, Adam Macdonald, Andrew The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title | The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title_full | The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title_fullStr | The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title_full_unstemmed | The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title_short | The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer |
title_sort | deubiquitinase (dub) usp13 promotes mcl-1 stabilisation in cervical cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979541/ https://www.ncbi.nlm.nih.gov/pubmed/33627786 http://dx.doi.org/10.1038/s41388-021-01679-8 |
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