IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8068.html
   My bibliography  Save this article

IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer

Author

Listed:
  • Rachel Tsui

    (Signaling Systems Laboratory, University of California
    The San Diego Center for Systems Biology, University of California
    University of California)

  • Jeffrey D. Kearns

    (Signaling Systems Laboratory, University of California
    University of California
    Present address: Merrimack Pharmaceuticals, Cambridge, MA 02139)

  • Candace Lynch

    (Signaling Systems Laboratory, University of California
    University of California
    Present address:The Scripps Research Institute, La Jolla, California 92037, USA)

  • Don Vu

    (University of California)

  • Kim A. Ngo

    (Signaling Systems Laboratory, University of California
    The San Diego Center for Systems Biology, University of California
    University of California)

  • Soumen Basak

    (Signaling Systems Laboratory, University of California
    University of California
    Present address:Systems Immunology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India)

  • Gourisankar Ghosh

    (University of California)

  • Alexander Hoffmann

    (Signaling Systems Laboratory, University of California
    The San Diego Center for Systems Biology, University of California
    University of California
    Immunology and Molecular Genetics (MIMG), Institute for Quantitative and Computational Biosciences (QCB), University of California)

Abstract

The NFκB family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NFκB dimer activity via the IκB–NFκB signalling module is well understood, there is little information on how specific dimer repertoires are generated from Rel family polypeptides. Here we report the iterative construction—guided by in vitro and in vivo experimentation—of a mathematical model of the Rel-NFκB generation module. Our study reveals that IκBβ has essential functions within the Rel-NFκB generation module, specifically for the RelA:RelA homodimer, which controls a subset of NFκB target genes. Our findings revise the current dogma of the three classical, functionally related IκB proteins by distinguishing between a positive ‘licensing’ factor (IκBβ) that contributes to determining the available NFκB dimer repertoire in a cell’s steady state, and negative feedback regulators (IκBα and -ɛ) that determine the duration and dynamics of the cellular response to an inflammatory stimulus.

Suggested Citation

  • Rachel Tsui & Jeffrey D. Kearns & Candace Lynch & Don Vu & Kim A. Ngo & Soumen Basak & Gourisankar Ghosh & Alexander Hoffmann, 2015. "IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8068
    DOI: 10.1038/ncomms8068
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8068
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8068?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:6:y:2015:i:1:d:10.1038_ncomms8068. 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.