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SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Ser62

Oncogene volume 35, pages 491–500 (2016)Cite this article

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Abstract

Serine 62 (Ser62) phosphorylation affects the c-Myc protein stability in cancer cells. However, the mechanism for dephosphorylating c-Myc is not well understood. In this study, we identified carboxyl-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (SCP1) as a novel phosphatase specifically dephosphorylating c-Myc Ser62. Ectopically expressed SCP1 strongly dephosphorylated c-Myc Ser62, destabilized c-Myc protein and suppressed c-Myc transcriptional activity. Knockdown of SCP1 increased the c-Myc protein levels in liver cancer cells. SCP1 interacted with c-Myc both in vivo and in vitro. In addition, Ser245 at the C-terminus of SCP1 was essential for its phosphatase activity towards c-Myc. Functionally, SCP1 negatively regulated the cancer cell proliferation. Collectively, our findings indicate that SCP1 is a potential tumor suppressor for liver cancers through dephosphorylating c-Myc Ser62.

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Acknowledgements

This work was supported by grants from National Basic Research Program of China (973 program 2012CB910404 and 2010CB529704), National Natural Science Foundation of China (30971521, 31171338 and 31222037), 'Shu Guang' project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (11SG27), Shanghai Key Laboratory of Regulatory Biology (11DZ2260300) and Shanghai Rising-Star program (09QA1401900 and 13QH1401300). PW is a scholar of the Program for New Century Excellent Talents in University (NCET-10-0387).

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Author notes

  1. W Wang and P Liao: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Central Laboratory, Shanghai 10th People's Hospital, Tongji University, Shanghai, China

    W Wang, P Liao, X Ge & P Wang

  2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

    W Wang, P Liao, M Shen, T Chen, Y Chen, Y Li & P Wang

  3. Department of Surgery, Baylor College of Medicine, Houston, TX, USA

    X Lin

  4. School of Life Science and Technology, Tongji University, Shanghai, China

    P Wang

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  1. W Wang
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Wang, W., Liao, P., Shen, M. et al. SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Ser62. Oncogene 35, 491–500 (2016). https://doi.org/10.1038/onc.2015.106

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