IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms13755.html
   My bibliography  Save this article

Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53

Author

Listed:
  • Tengfei Chao

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine
    Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)

  • Xiang Zhou

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine
    Present address: Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China)

  • Bo Cao

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine)

  • Peng Liao

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine)

  • Hongbing Liu

    (Tulane University School of Medicine
    Present address: Department of Pediatrics, Tulane University School of Medicine; New Orleans, Louisiana 70112, USA)

  • Yun Chen

    (Tulane University School of Medicine)

  • Hee-Won Park

    (Tulane University School of Medicine)

  • Shelya X. Zeng

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine)

  • Hua Lu

    (Tulane University School of Medicine
    Tulane Cancer Center, Tulane University School of Medicine)

Abstract

The tumour suppressor p53 transactivates the expression of its target genes to exert its functions. Here, we identify a pleckstrin homology domain-containing protein (PHLDB3)-encoding gene as a p53 target. PHLDB3 overexpression increases proliferation and restrains apoptosis of wild-type p53-harboring cancer cells by reducing p53 protein levels. PHLDB3 binds to MDM2 (mouse double minute 2 homolog) and facilitates MDM2-mediated ubiquitination and degradation of p53. Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil. Analysis of cancer genomic databases reveals that PHLDB3 is amplified and/or highly expressed in numerous human cancers. Altogether, these results demonstrate that PHLDB3 promotes tumour growth by inactivating p53 in a negative feedback fashion and suggest PHLDB3 as a potential therapeutic target in various human cancers.

Suggested Citation

  • Tengfei Chao & Xiang Zhou & Bo Cao & Peng Liao & Hongbing Liu & Yun Chen & Hee-Won Park & Shelya X. Zeng & Hua Lu, 2016. "Pleckstrin homology domain-containing protein PHLDB3 supports cancer growth via a negative feedback loop involving p53," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13755
    DOI: 10.1038/ncomms13755
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13755
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13755?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13755. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.