Oscillations in NF-κB signaling control the dynamics of gene expression

D. E. Nelson, A. E C Ihekwaba, M. Elliott, J. R. Johnson, C. A. Gibney, B. E. Foreman, C. Nelson, V. See, C. A. Horton, D. G. Spiller, S. W. Edwards, H. P. McDowell, J. F. Unitt, E. Sullivan, R. Grimley, N. Benson, D. Broomhead, D. B. Kell, M. R H White

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Signaling by the transcription factor nuclear factor kappa B (NF-κB) involves its release from inhibitor kappa B (IκB) in the cytosol, followed by translocation into the nucleus. NF-κB regulation of IκBα transcription represents a delayed negative feedback loop that drives oscillations in NF-κB translocation. Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IκBα transcription. Transcription of target genes depended on oscillation persistence, involving cycles of RelA phosphorylation and dephosphorylation. The functional consequences of NF-κB signaling may thus depend on number, period, and amplitude of oscillations.
    Original languageEnglish
    Pages (from-to)704-708
    Number of pages4
    JournalScience
    Volume306
    Issue number5696
    DOIs
    Publication statusPublished - 22 Oct 2004

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