IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03117-y.html
   My bibliography  Save this article

EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase

Author

Listed:
  • Kousuke Kasahara

    (Mie University Graduate School of Medicine)

  • Hiromasa Aoki

    (Nagoya City University)

  • Tohru Kiyono

    (National Cancer Center Research Institute)

  • Shujie Wang

    (Mie University Graduate School of Medicine)

  • Harumi Kagiwada

    (National Institute of Advanced Industrial Science and Technology)

  • Mizuki Yuge

    (Mie University Graduate School of Medicine)

  • Toshio Tanaka

    (Mie University Graduate School of Medicine)

  • Yuhei Nishimura

    (Mie University Graduate School of Medicine)

  • Akira Mizoguchi

    (Mie University Graduate School of Medicine)

  • Naoki Goshima

    (National Institute of Advanced Industrial Science and Technology)

  • Masaki Inagaki

    (Mie University Graduate School of Medicine)

Abstract

Ciliogenesis is generally inhibited in dividing cells, however, it has been unclear which signaling cascades regulate the phenomenon. Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells. These phosphorylations elevate the deubiquitinase activity, which then stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through downregulation of the USP8-trichoplein-Aurora A signal. Moreover, primary cilia abrogation, which is induced upon IFT20 or Cep164 depletion, ameliorates the cell cycle arrest of EGFR knockdown cells. The present data reveal that the EGFR-USP8-trichoplein-Aurora A axis is a critical signaling cascade that restricts ciliogenesis in dividing cells, and functions to facilitate cell proliferation. We further show that usp8 knockout zebrafish develops ciliopathy-related phenotypes including cystic kidney, suggesting that USP8 is a regulator of ciliogenesis in vertebrates.

Suggested Citation

  • Kousuke Kasahara & Hiromasa Aoki & Tohru Kiyono & Shujie Wang & Harumi Kagiwada & Mizuki Yuge & Toshio Tanaka & Yuhei Nishimura & Akira Mizoguchi & Naoki Goshima & Masaki Inagaki, 2018. "EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03117-y
    DOI: 10.1038/s41467-018-03117-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03117-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03117-y?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_s41467-018-03117-y. 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.