1. Cancer Biology
  2. Cell Biology

Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator

  1. Xiang Zhou
  2. Qian Hao
  3. Peng Liao
  4. Shiwen Luo
  5. Minhong Zhang
  6. Guohui hu
  7. Hongbing Liu
  8. Yiwei Zhang
  9. Bo Cao
  10. Melody Baddoo
  11. Erik K Flemington
  12. Shelya X Zeng
  13. Hua Lu  Is a corresponding author
  1. Fudan University, China
  2. Tulane University School of Medicine, United States
  3. The First Affiliated Hospital of Nanchang University, China
https://doi.org/10.7554/eLife.15099
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  1. Xiang Zhou
  2. Qian Hao
  3. Peng Liao
  4. Shiwen Luo
  5. Minhong Zhang
  6. Guohui hu
  7. Hongbing Liu
  8. Yiwei Zhang
  9. Bo Cao
  10. Melody Baddoo
  11. Erik K Flemington
  12. Shelya X Zeng
  13. Hua Lu
(2016)
Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator
eLife 5:e15099.
https://doi.org/10.7554/eLife.15099
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  3. Download .RIS

Abstract

Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, CD271 or p75NTR) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2-mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth. NGFR is highly expressed in human glioblastomas, and its gene is often amplified in breast cancers with wild type p53. Altogether, our results demonstrate that cancers hijack NGFR as an oncogenic inhibitor of p53.

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Author details

  1. Xiang Zhou

    Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Qian Hao

    Shanghai Cancer Center, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Peng Liao

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Shiwen Luo

    Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Minhong Zhang

    Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Guohui hu

    Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Hongbing Liu

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Yiwei Zhang

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Bo Cao

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Melody Baddoo

    Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Erik K Flemington

    Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Shelya X Zeng

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.

  13. Hua Lu

    Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, United States
    For correspondence
    hlu2@tulane.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Carol Prives, Columbia University, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#4257R) of Tulane University School of Medicine.

Version history

  1. Received: February 8, 2016
  2. Accepted: June 9, 2016
  3. Accepted Manuscript published: June 10, 2016 (version 1)
  4. Version of Record published: July 13, 2016 (version 2)

Copyright

© 2016, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xiang Zhou
  2. Qian Hao
  3. Peng Liao
  4. Shiwen Luo
  5. Minhong Zhang
  6. Guohui hu
  7. Hongbing Liu
  8. Yiwei Zhang
  9. Bo Cao
  10. Melody Baddoo
  11. Erik K Flemington
  12. Shelya X Zeng
  13. Hua Lu
(2016)
Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator
eLife 5:e15099.
https://doi.org/10.7554/eLife.15099

Share this article

https://doi.org/10.7554/eLife.15099

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