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

1
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha 410082, China
2
School of Life Sciences, Central South University, Changsha 410078, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(4), 297; https://doi.org/10.3390/cells8040297
Received: 10 February 2019 / Revised: 18 March 2019 / Accepted: 26 March 2019 / Published: 31 March 2019
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
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. View Full-Text
Keywords: deubiquitination; cell cycle; DUB3; cyclin A deubiquitination; cell cycle; DUB3; cyclin A
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Hu, B.; Deng, T.; Ma, H.; Liu, Y.; Feng, P.; Wei, D.; Ling, N.; Li, L.; Qiu, S.; Zhang, L.; Peng, B.; Liu, J.; Ye, M. Deubiquitinase DUB3 Regulates Cell Cycle Progression via Stabilizing Cyclin A for Proliferation of Non-Small Cell Lung Cancer Cells. Cells 2019, 8, 297.

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