Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression

D. E. Nelson, Adaoha Ihekwaba, M. Elliott, J.R. Johnson, C.A. Gibney, B.E. Foreman, G. 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 Bell, M.R.H. White

Research output: Contribution to journalArticlepeer-review

939 Citations (Scopus)

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
Article number5696
Pages (from-to)704-708
Number of pages5
JournalScience
Volume306
Issue number5696
DOIs
Publication statusPublished - 22 Oct 2004
Externally publishedYes

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