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Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission
Dynamin‐related protein 1 (Drp1) is a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases, including cancer. However, the regulation of Drp1, especially of its ubiquitination, remains unclear. In this study, we report t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718948/ https://www.ncbi.nlm.nih.gov/pubmed/33070427 http://dx.doi.org/10.1002/1878-0261.12825 |
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author | Shi, Le Liu, Jing Peng, Yunhua Zhang, Jinfang Dai, Xiangpeng Zhang, Shuangxi Wang, Yongyao Liu, Jiankang Long, Jiangang |
author_facet | Shi, Le Liu, Jing Peng, Yunhua Zhang, Jinfang Dai, Xiangpeng Zhang, Shuangxi Wang, Yongyao Liu, Jiankang Long, Jiangang |
author_sort | Shi, Le |
collection | PubMed |
description | Dynamin‐related protein 1 (Drp1) is a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases, including cancer. However, the regulation of Drp1, especially of its ubiquitination, remains unclear. In this study, we report that the ovarian tumor‐associated protease deubiquitinase 6A (OTUD6A) deubiquitylates and stabilizes Drp1, thereby facilitating regulation of mitochondrial morphology and tumorigenesis. OTUD6A is upregulated in human patients with colorectal cancer. The depletion of OTUD6A leads to lower Drp1 levels and suppressed mitochondrial fission, and the affected cells are consequently less prone to tumorigenesis. Conversely, the overexpression of OTUD6A increases Drp1 levels and its protein half‐life and enhances cancer cell growth. Therefore, our results reveal a novel upstream protein of Drp1, and its role in tumorigenesis that is played, in part, through the activation of mitochondrial fission mediated by Drp1. |
format | Online Article Text |
id | pubmed-7718948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77189482020-12-11 Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission Shi, Le Liu, Jing Peng, Yunhua Zhang, Jinfang Dai, Xiangpeng Zhang, Shuangxi Wang, Yongyao Liu, Jiankang Long, Jiangang Mol Oncol Research Articles Dynamin‐related protein 1 (Drp1) is a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases, including cancer. However, the regulation of Drp1, especially of its ubiquitination, remains unclear. In this study, we report that the ovarian tumor‐associated protease deubiquitinase 6A (OTUD6A) deubiquitylates and stabilizes Drp1, thereby facilitating regulation of mitochondrial morphology and tumorigenesis. OTUD6A is upregulated in human patients with colorectal cancer. The depletion of OTUD6A leads to lower Drp1 levels and suppressed mitochondrial fission, and the affected cells are consequently less prone to tumorigenesis. Conversely, the overexpression of OTUD6A increases Drp1 levels and its protein half‐life and enhances cancer cell growth. Therefore, our results reveal a novel upstream protein of Drp1, and its role in tumorigenesis that is played, in part, through the activation of mitochondrial fission mediated by Drp1. John Wiley and Sons Inc. 2020-11-06 2020-12 /pmc/articles/PMC7718948/ /pubmed/33070427 http://dx.doi.org/10.1002/1878-0261.12825 Text en © 2020 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Shi, Le Liu, Jing Peng, Yunhua Zhang, Jinfang Dai, Xiangpeng Zhang, Shuangxi Wang, Yongyao Liu, Jiankang Long, Jiangang Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title | Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title_full | Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title_fullStr | Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title_full_unstemmed | Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title_short | Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission |
title_sort | deubiquitinase otud6a promotes proliferation of cancer cells via regulating drp1 stability and mitochondrial fission |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718948/ https://www.ncbi.nlm.nih.gov/pubmed/33070427 http://dx.doi.org/10.1002/1878-0261.12825 |
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