IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-24792-4.html
   My bibliography  Save this article

The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium

Author

Listed:
  • Chloé Maurizy

    (CNRS
    Equipe labélisée Ligue Nationale Contre le Cancer)

  • Claire Abeza

    (CNRS
    Equipe labélisée Ligue Nationale Contre le Cancer)

  • Bénédicte Lemmers

    (CNRS)

  • Monica Gabola

    (CNRS)

  • Ciro Longobardi

    (CNRS)

  • Valérie Pinet

    (CNRS)

  • Marina Ferrand

    (CNRS)

  • Conception Paul

    (CNRS)

  • Julie Bremond

    (CNRS)

  • Francina Langa

    (Institut Pasteur)

  • François Gerbe

    (Equipe labélisée Ligue Nationale Contre le Cancer
    INSERM)

  • Philippe Jay

    (Equipe labélisée Ligue Nationale Contre le Cancer
    INSERM)

  • Céline Verheggen

    (CNRS
    Equipe labélisée Ligue Nationale Contre le Cancer
    CNRS)

  • Nicola Tinari

    (‘G. d’Annunzio’ University of Chieti–Pescara)

  • Dominique Helmlinger

    (CNRS)

  • Rossano Lattanzio

    (‘G. d’Annunzio’ University of Chieti–Pescara)

  • Edouard Bertrand

    (CNRS
    Equipe labélisée Ligue Nationale Contre le Cancer
    CNRS)

  • Michael Hahne

    (CNRS)

  • Bérengère Pradet-Balade

    (Equipe labélisée Ligue Nationale Contre le Cancer
    CNRS)

Abstract

The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice for Rpap3 to inactivate this core component of R2TP in the intestinal epithelium. In adult mice, Rpap3 invalidation caused destruction of the small intestinal epithelium and death within 10 days. Levels of R2TP substrates decreased, with strong effects on mTOR, ATM and ATR. Proliferative stem cells and progenitors deficient for Rpap3 failed to import RNA polymerase II into the nucleus and they induced p53, cell cycle arrest and apoptosis. Post-mitotic, differentiated cells did not display these alterations, suggesting that R2TP clients are preferentially built in actively proliferating cells. In addition, high RPAP3 levels in colorectal tumors from patients correlate with bad prognosis. Here, we show that, in the intestine, the R2TP chaperone plays essential roles in normal and tumoral proliferation.

Suggested Citation

  • Chloé Maurizy & Claire Abeza & Bénédicte Lemmers & Monica Gabola & Ciro Longobardi & Valérie Pinet & Marina Ferrand & Conception Paul & Julie Bremond & Francina Langa & François Gerbe & Philippe Jay &, 2021. "The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24792-4
    DOI: 10.1038/s41467-021-24792-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-24792-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-24792-4?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:12:y:2021:i:1:d:10.1038_s41467-021-24792-4. 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.