The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation

DOI Web Site 被引用文献29件
  • Alexander Hoffmann
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
  • Andre Levchenko
    Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Martin L. Scott
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • David Baltimore
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

説明

<jats:p> Nuclear localization of the transcriptional activator NF-κB (nuclear factor κB) is controlled in mammalian cells by three isoforms of NF-κB inhibitor protein: IκBα, -β, and - <jats:italic>ɛ</jats:italic> . Based on simplifying reductions of the IκB–NF-κB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-κB activation by the coordinated degradation and synthesis of IκB proteins. The model demonstrates that IκBα is responsible for strong negative feedback that allows for a fast turn-off of the NF-κB response, whereas IκBβ and - <jats:italic>ɛ</jats:italic> function to reduce the system's oscillatory potential and stabilize NF-κB responses during longer stimulations. Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression. </jats:p>

収録刊行物

  • Science

    Science 298 (5596), 1241-1245, 2002-11-08

    American Association for the Advancement of Science (AAAS)

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