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 Kell; M.R.H. White

doi:10.1126/science.1099962

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 Kell, M.R.H. White

Research output: Contribution to journal › Article › peer-review

1029 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 language	English
Article number	5696
Pages (from-to)	704-708
Number of pages	5
Journal	Science
Volume	306
Issue number	5696
DOIs	https://doi.org/10.1126/science.1099962
Publication status	Published - 22 Oct 2004
Externally published	Yes

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Nelson, D. E., Ihekwaba, A., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., Nelson, G., See, V., Horton, C. A., Spiller, D. G., Edwards, S. W., McDowell, H. P., Unitt, J. F., Sullivan, E., Grimley, R., Benson, N., Broomhead, D., Kell, D. B., & White, M. R. H. (2004). Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression. Science, 306(5696), 704-708. Article 5696. https://doi.org/10.1126/science.1099962

Nelson, DE, Ihekwaba, A, Elliott, M, Johnson, JR, Gibney, CA, Foreman, BE, Nelson, G, See, V, Horton, CA, Spiller, DG, Edwards, SW, McDowell, HP, Unitt, JF, Sullivan, E, Grimley, R, Benson, N, Broomhead, D, Kell, DB & White, MRH 2004, 'Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression', Science, vol. 306, no. 5696, 5696, pp. 704-708. https://doi.org/10.1126/science.1099962

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title = "Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression",

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.",

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

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AU - Nelson, D. E.

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AU - Gibney, C.A.

AU - Foreman, B.E.

AU - Nelson, G.

AU - See, V.

AU - Horton, C.A.

AU - Spiller, D.G.

AU - Edwards, S.W.

AU - McDowell, H. P.

AU - Unitt, J. F.

AU - Sullivan, E.

AU - Grimley, R.

AU - Benson, N.

AU - Broomhead, D.

AU - Kell, D.B

AU - White, M.R.H.

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N2 - 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.

AB - 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.

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DO - 10.1126/science.1099962

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ER -

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

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