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The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53

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Abstract

Human glioma causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying glioma progression are still largely unknown. COP1 (constitutively photomorphogenic 1), an E3 ubiquitin ligase, is important in cell survival, development, cell growth, and cancer biology by regulating different substrates. As is well known, both tumor suppressor p53 and oncogenic protein c-JUN could be ubiquitinated and degraded by ubiquitin ligase COP1, which may be the reason that COP1 serves as an oncogene or a tumor suppressor in different cancer types. Up to now, the possible role of COP1 in human glioma is still unclear. In the present study, we found that the expression of COP1 was upregulated in human glioma tissues. The role of COP1 in glioma cell proliferation was investigated using COP1 loss- and gain-of-function. The results showed that downregulation of COP1 by short hairpin RNA (shRNA) inhibited glioma cell proliferation, while overexpression of COP1 significantly promoted it. Furthermore, we demonstrated that COP1 only interacted with and regulated p53, but not c-JUN. Taken together, these results indicate that COP1 may play a role in promoting glioma cell proliferation by interacting with and downregulating tumor suppressor p53 rather than oncogenic protein c-JUN.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81472345 and 81400127), the Natural Science Foundation of Jiangsu Province of China (BK20151165), the China Postdoctoral Science Foundation (2014M551662 and 2016T90507), and the Jiangsu Planned Projects for Postdoctoral Research Funds (1302111B and 1402191C).

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Authors and Affiliations

  1. Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People’s Republic of China

    Shenshan Zou, Yufu Zhu, Bin Wang, Fengyuan Qian, Xiang Zhang, Lei Wang, Hanmo Bao, Manyi Xie, Shangfeng Gao, Rutong Yu & Hengliang Shi

  2. The Graduate School, Xuzhou Medical College, Xuzhou, China

    Shenshan Zou, Bin Wang, Fengyuan Qian, Xiang Zhang & Hanmo Bao

  3. Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People’s Republic of China

    Yufu Zhu, Lei Wang, Manyi Xie, Shangfeng Gao, Rutong Yu & Hengliang Shi

  4. Institute of Blood Diseases, Xuzhou Medical College, Xuzhou, China

    Chunling Fu

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  1. Shenshan Zou
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Correspondence to Rutong Yu or Hengliang Shi.

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Shenshan Zou and Yufu Zhu contributed equally to this work.

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Zou, S., Zhu, Y., Wang, B. et al. The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53. Mol Neurobiol 54, 5008–5016 (2017). https://doi.org/10.1007/s12035-016-0033-x

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