IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v3y2012i1d10.1038_ncomms1975.html
   My bibliography  Save this article

Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway

Author

Listed:
  • Azadeh Arabi

    (Karolinska Institutet, 171 77 Stockholm, Sweden.)

  • Karim Ullah

    (Karolinska Institutet, 171 77 Stockholm, Sweden.)

  • Rui M.M. Branca

    (Clinical Proteomics Mass Spectrometry, Science for Life Laboratory, Solna 171 21, Sweden.
    Karolinska Institutet, Stockholm 17176, Sweden.)

  • Johan Johansson

    (Swedish Defence, Stockholm 10251, Sweden.)

  • Daniel Bandarra

    (Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, United Kingdom.)

  • Moritz Haneklaus

    (Karolinska Institutet, Stockholm 17176, Sweden.)

  • Jing Fu

    (University of Pittsburgh Cancer Institute, School of Medicine)

  • Ingrid Ariës

    (Rotterdam 3000 CB, The Netherlands.
    Rotterdam 3000 CB, The Netherlands.)

  • Peter Nilsson

    (Science for Life Laboratory, School of Biotechnology KTH, Royal Institute of Technology, Stockholm 171 21, Sweden.)

  • Monique L. Den Boer

    (Rotterdam 3000 CB, The Netherlands.
    Rotterdam 3000 CB, The Netherlands.)

  • Katja Pokrovskaja

    (Karolinska Institutet, Stockholm 17176, Sweden.)

  • Dan Grandér

    (Karolinska Institutet, Stockholm 17176, Sweden.)

  • Gutian Xiao

    (University of Pittsburgh Cancer Institute, School of Medicine)

  • Sonia Rocha

    (Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, United Kingdom.)

  • Janne Lehtiö

    (Clinical Proteomics Mass Spectrometry, Science for Life Laboratory, Solna 171 21, Sweden.
    Karolinska Institutet, Stockholm 17176, Sweden.)

  • Olle Sangfelt

    (Karolinska Institutet, 171 77 Stockholm, Sweden.)

Abstract

Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several disease-associated proteins. The transcription factor NF-κB2 (p100/p52) is one of the candidate Fbw7 substrates. We show that Fbw7 interacts with p100 via a conserved degron and that it promotes degradation of p100 in a GSK3β phosphorylation-dependent manner. Fbw7 inactivation increases p100 levels, which in the presence of NF-κB pathway stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic threshold can be increased by loss of Fbw7 in a p100-dependent manner. In conclusion, Fbw7-mediated destruction of p100 is a regulatory component restricting the response to NF-κB2 pathway stimulation.

Suggested Citation

  • Azadeh Arabi & Karim Ullah & Rui M.M. Branca & Johan Johansson & Daniel Bandarra & Moritz Haneklaus & Jing Fu & Ingrid Ariës & Peter Nilsson & Monique L. Den Boer & Katja Pokrovskaja & Dan Grandér & G, 2012. "Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1975
    DOI: 10.1038/ncomms1975
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms1975
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms1975?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:3:y:2012:i:1:d:10.1038_ncomms1975. 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.