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Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells

The deubiquitinase DUB3 is frequently overexpressed in non-small cell lung cancer (NSCLC) and contributes to its malignant phenotype. However, the underlying molecular mechanism of DUB3 in NSCLC is largely unknown. In this study, we report that DUB3 regulates cell cycle progression by deubiquitinati...

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Autores principales: Hu, Bin, Deng, Tanggang, Ma, Hongchang, Liu, Yan, Feng, Peifu, Wei, Dong, Ling, Neng, Li, Ling, Qiu, Siyuan, Zhang, Lin, Peng, Bo, Liu, Jing, Ye, Mao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523561/
https://www.ncbi.nlm.nih.gov/pubmed/30935108
http://dx.doi.org/10.3390/cells8040297
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author Hu, Bin
Deng, Tanggang
Ma, Hongchang
Liu, Yan
Feng, Peifu
Wei, Dong
Ling, Neng
Li, Ling
Qiu, Siyuan
Zhang, Lin
Peng, Bo
Liu, Jing
Ye, Mao
author_facet Hu, Bin
Deng, Tanggang
Ma, Hongchang
Liu, Yan
Feng, Peifu
Wei, Dong
Ling, Neng
Li, Ling
Qiu, Siyuan
Zhang, Lin
Peng, Bo
Liu, Jing
Ye, Mao
author_sort Hu, Bin
collection PubMed
description The deubiquitinase DUB3 is frequently overexpressed in non-small cell lung cancer (NSCLC) and contributes to its malignant phenotype. However, the underlying molecular mechanism of DUB3 in NSCLC is largely unknown. In this study, we report that DUB3 regulates cell cycle progression by deubiquitinating cyclin A that links to proliferation of NSCLC cells. We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels. Mechanistically, DUB3 interacts with cyclin A, which removes the polyubiquitin chains conjugated onto cyclin A and stabilizes the cyclin A protein. Furthermore, we demonstrate that DUB3 regulates cell cycle progression by stabilizing cyclin A, because ablation of DUB3 arrests cell cycle from G0/G1 to S phase and the resulting effect can be rescued by introducing cyclin A into NSCLC cells. Functionally, we found that the effect of DUB3 on cyclin A mediates proliferation of NSCLC cells. Moreover, a significant correlation between DUB3 abundance and cyclin A expression levels were also found in NSCLC samples. Taken together, these results reveal that DUB3 functions as a novel cyclin A regulator through maintaining cyclin A stability, and that the DUB3-cyclin A signaling axis plays a critical role in cell cycle progression for proliferation of NSCLC.
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spelling pubmed-65235612019-06-03 Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells Hu, Bin Deng, Tanggang Ma, Hongchang Liu, Yan Feng, Peifu Wei, Dong Ling, Neng Li, Ling Qiu, Siyuan Zhang, Lin Peng, Bo Liu, Jing Ye, Mao Cells Article The deubiquitinase DUB3 is frequently overexpressed in non-small cell lung cancer (NSCLC) and contributes to its malignant phenotype. However, the underlying molecular mechanism of DUB3 in NSCLC is largely unknown. In this study, we report that DUB3 regulates cell cycle progression by deubiquitinating cyclin A that links to proliferation of NSCLC cells. We found that knockdown of DUB3 decreases cyclin A levels, whereas overexpression of DUB3 strongly increases cyclin A levels. Mechanistically, DUB3 interacts with cyclin A, which removes the polyubiquitin chains conjugated onto cyclin A and stabilizes the cyclin A protein. Furthermore, we demonstrate that DUB3 regulates cell cycle progression by stabilizing cyclin A, because ablation of DUB3 arrests cell cycle from G0/G1 to S phase and the resulting effect can be rescued by introducing cyclin A into NSCLC cells. Functionally, we found that the effect of DUB3 on cyclin A mediates proliferation of NSCLC cells. Moreover, a significant correlation between DUB3 abundance and cyclin A expression levels were also found in NSCLC samples. Taken together, these results reveal that DUB3 functions as a novel cyclin A regulator through maintaining cyclin A stability, and that the DUB3-cyclin A signaling axis plays a critical role in cell cycle progression for proliferation of NSCLC. MDPI 2019-03-31 /pmc/articles/PMC6523561/ /pubmed/30935108 http://dx.doi.org/10.3390/cells8040297 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hu, Bin
Deng, Tanggang
Ma, Hongchang
Liu, Yan
Feng, Peifu
Wei, Dong
Ling, Neng
Li, Ling
Qiu, Siyuan
Zhang, Lin
Peng, Bo
Liu, Jing
Ye, Mao
Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title_full Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title_fullStr Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title_full_unstemmed Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title_short Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells
title_sort deubiquitinase dub3 regulates cell cycle progression via stabilizing cyclin a for proliferation of non-small cell lung cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523561/
https://www.ncbi.nlm.nih.gov/pubmed/30935108
http://dx.doi.org/10.3390/cells8040297
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