Sci. Signal., 20 October 2009
Vol. 2, Issue 93, p. ra65
[DOI: 10.1126/scisignal.2000599]

RESEARCH ARTICLES

Editor's Summary

Prolonging NF-B Activation

Regulation of the activity of the transcription factor NF-B, which plays key roles in immune responses, exhibits complicated cellular dynamics. Tumor necrosis factor– (TNF-), a proinflammatory cytokine that activates the death-domain receptor TNFR, and lipopolysaccharide (LPS), a pathogen-derived molecule that activates the Toll-like receptor TLR4, both activate NF-B. Lee et al. provide a mechanism by which cells respond to these two ligands with different kinetics. Cells responding to TNF- exhibit an oscillating translocation of NF-B in and out of the nucleus, with all cells responding similarly. In contrast, cells responding to LPS showed two distinct modes, with one population exhibiting transient nuclear localization of NF-B and a second exhibiting persistent nuclear localization. Lee et al. modified an existing computational model of the pathways that activate NF-B and found that cells responding to LPS produce TNF- in concentrations that are low enough that only a subset of neighboring cells responds. This paracrine TNF- signal produces the population of LPS-responsive cells with persistent prolonged NF-B activation.

Citation: T. K. Lee, E. M. Denny, J. C. Sanghvi, J. E. Gaston, N. D. Maynard, J. J. Hughey, M. W. Covert, A Noisy Paracrine Signal Determines the Cellular NF-B Response to Lipopolysaccharide. Sci. Signal. 2, ra65 (2009).

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Tunable Signal Processing Through Modular Control of Transcription Factor Translocation.

N. Hao, B. A. Budnik, J. Gunawardena, and E. K. O'Shea (2013)
Science 339, 460-464
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TWEAK and cIAP1 Regulate Myoblast Fusion Through the Noncanonical NF-{kappa}B Signaling Pathway.

E. K. Enwere, J. Holbrook, R. Lejmi-Mrad, J. Vineham, K. Timusk, B. Sivaraj, M. Isaac, D. Uehling, R. Al-awar, E. LaCasse, et al. (2012)
Science Signaling 5, ra75
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Interrogation of Inhibitor of Nuclear Factor {kappa}B {alpha}/Nuclear Factor {kappa}B (I{kappa}B{alpha}/NF-{kappa}B) Negative Feedback Loop Dynamics: FROM SINGLE CELLS TO LIVE ANIMALS IN VIVO.

B. L. Moss, A. Elhammali, T. Fowlkes, S. Gross, A. Vinjamoori, C. H. Contag, and D. Piwnica-Worms (2012)
J. Biol. Chem. 287, 31359-31370
 |  Abstract »  |  Full Text »  |  PDF »

p53 Dynamics Control Cell Fate.

J. E. Purvis, K. W. Karhohs, C. Mock, E. Batchelor, A. Loewer, and G. Lahav (2012)
Science 336, 1440-1444
 |  Abstract »  |  Full Text »  |  PDF »

Spatiotemporal Inhibition of Innate Immunity Signaling by the Tbc1d23 RAB-GAP.

L. De Arras, I. V. Yang, B. Lackford, D. W. H. Riches, R. Prekeris, J. H. Freedman, D. A. Schwartz, and S. Alper (2012)
J. Immunol. 188, 2905-2913
 |  Abstract »  |  Full Text »  |  PDF »

Akt Fine-tunes NF-{kappa}B-dependent Gene Expression during T Cell Activation.

J. Cheng, B. Phong, D. C. Wilson, R. Hirsch, and L. P. Kane (2011)
J. Biol. Chem. 286, 36076-36085
 |  Abstract »  |  Full Text »  |  PDF »

Physiological levels of TNF{alpha} stimulation induce stochastic dynamics of NF-{kappa}B responses in single living cells.

D. A. Turner, P. Paszek, D. J. Woodcock, D. E. Nelson, C. A. Horton, Y. Wang, D. G. Spiller, D. A. Rand, M. R. H. White, and C. V. Harper (2010)
J. Cell Sci. 123, 2834-2843
 |  Abstract »  |  Full Text »  |  PDF »

Population robustness arising from cellular heterogeneity.

P. Paszek, S. Ryan, L. Ashall, K. Sillitoe, C. V. Harper, D. G. Spiller, D. A. Rand, and M. R. H. White (2010)
PNAS 107, 11644-11649
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Science Signaling Podcast: 5 January 2010.

M. B. Yaffe and A. M. VanHook (2010)
Science Signaling 3, pc1
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