IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03327-4.html
   My bibliography  Save this article

Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression

Author

Listed:
  • Lingdi Zhang

    (University of Colorado Denver Anschutz Medical Campus)

  • Hengbo Zhou

    (University of Colorado Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus)

  • Xueni Li

    (University of Colorado Denver Anschutz Medical Campus)

  • Rebecca L Vartuli

    (University of Colorado Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus)

  • Michael Rowse

    (University of Wisconsin-Madison)

  • Yongna Xing

    (University of Wisconsin-Madison)

  • Pratyaydipta Rudra

    (University of Colorado Anschutz Medical Campus)

  • Debashis Ghosh

    (University of Colorado Anschutz Medical Campus)

  • Rui Zhao

    (University of Colorado Denver Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus)

  • Heide L Ford

    (University of Colorado Denver Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus
    University of Colorado Anschutz Medical Campus)

Abstract

Eya genes encode a unique family of multifunctional proteins that serve as transcriptional co-activators and as haloacid dehalogenase-family Tyr phosphatases. Intriguingly, the N-terminal domain of Eyas, which does not share sequence similarity to any known phosphatases, contains a separable Ser/Thr phosphatase activity. Here, we demonstrate that the Ser/Thr phosphatase activity of Eya is not intrinsic, but arises from its direct interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme. Importantly, Eya3 alters the regulation of c-Myc by PP2A, increasing c-Myc stability by enabling PP2A-B55α to dephosphorylate pT58, in direct contrast to the previously described PP2A-B56α-mediated dephosphorylation of pS62 and c-Myc destabilization. Furthermore, Eya3 and PP2A-B55α promote metastasis in a xenograft model of breast cancer, opposing the canonical tumor suppressive function of PP2A-B56α. Our study identifies Eya3 as a regulator of PP2A, a major cellular Ser/Thr phosphatase, and uncovers a mechanism of controlling the stability of a critical oncogene, c-Myc.

Suggested Citation

  • Lingdi Zhang & Hengbo Zhou & Xueni Li & Rebecca L Vartuli & Michael Rowse & Yongna Xing & Pratyaydipta Rudra & Debashis Ghosh & Rui Zhao & Heide L Ford, 2018. "Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03327-4
    DOI: 10.1038/s41467-018-03327-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03327-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03327-4?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:9:y:2018:i:1:d:10.1038_s41467-018-03327-4. 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.