IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06854-2.html
   My bibliography  Save this article

Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1

Author

Listed:
  • Salima Daou

    (University of Montréal
    Sinai Health System)

  • Haithem Barbour

    (University of Montréal)

  • Oumaima Ahmed

    (University of Montréal)

  • Louis Masclef

    (University of Montréal)

  • Caroline Baril

    (University of Montréal)

  • Nadine Nkwe

    (University of Montréal)

  • Daméhan Tchelougou

    (University of Montréal)

  • Maxime Uriarte

    (University of Montréal)

  • Eric Bonneil

    (University of Montréal)

  • Derek Ceccarelli

    (Sinai Health System)

  • Nazar Mashtalir

    (University of Montréal)

  • Mika Tanji

    (University of Hawaii Cancer Center, University of Hawaii)

  • Jean-Yves Masson

    (Laval University Cancer Research Center, 9 McMahon)

  • Pierre Thibault

    (University of Montréal)

  • Frank Sicheri

    (Sinai Health System)

  • Haining Yang

    (University of Hawaii Cancer Center, University of Hawaii)

  • Michele Carbone

    (University of Hawaii Cancer Center, University of Hawaii)

  • Marc Therrien

    (University of Montréal
    University of Montréal)

  • El Bachir Affar

    (University of Montréal)

Abstract

The tumor suppressor and deubiquitinase (DUB) BAP1 and its Drosophila ortholog Calypso assemble DUB complexes with the transcription regulators Additional sex combs-like (ASXL1, ASXL2, ASXL3) and Asx respectively. ASXLs and Asx use their DEUBiquitinase ADaptor (DEUBAD) domain to stimulate BAP1/Calypso DUB activity. Here we report that monoubiquitination of the DEUBAD is a general feature of ASXLs and Asx. BAP1 promotes DEUBAD monoubiquitination resulting in an increased stability of ASXL2, which in turn stimulates BAP1 DUB activity. ASXL2 monoubiquitination is directly catalyzed by UBE2E family of Ubiquitin-conjugating enzymes and regulates mammalian cell proliferation. Remarkably, Calypso also regulates Asx monoubiquitination and transgenic flies expressing monoubiquitination-defective Asx mutant exhibit developmental defects. Finally, the protein levels of ASXL2, BAP1 and UBE2E enzymes are highly correlated in mesothelioma tumors suggesting the importance of this signaling axis for tumor suppression. We propose that monoubiquitination orchestrates a molecular symbiosis relationship between ASXLs and BAP1.

Suggested Citation

  • Salima Daou & Haithem Barbour & Oumaima Ahmed & Louis Masclef & Caroline Baril & Nadine Nkwe & Daméhan Tchelougou & Maxime Uriarte & Eric Bonneil & Derek Ceccarelli & Nazar Mashtalir & Mika Tanji & Je, 2018. "Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1," Nature Communications, Nature, vol. 9(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06854-2
    DOI: 10.1038/s41467-018-06854-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06854-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06854-2?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nidhi Rohatgi & Wei Zou & Yongjia Li & Kevin Cho & Patrick L. Collins & Eric Tycksen & Gaurav Pandey & Carl J. DeSelm & Gary J. Patti & Anwesha Dey & Steven L. Teitelbaum, 2023. "BAP1 promotes osteoclast function by metabolic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    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_s41467-018-06854-2. 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.