Cracking the NF-κB Code

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Sci. Signal.  18 Feb 2014:
Vol. 7, Issue 313, pp. pe5
DOI: 10.1126/scisignal.2005108

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The discovery of feedback loops between signaling and gene expression is ushering in new quantitative models of cellular regulation. In a recent issue of Science Signaling, Sung et al. showed how positive feedback downstream of nuclear factor κB (NF-κB) signaling enhances the capacity of macrophages to scale their antimicrobial responses to the dose of pathogen-associated molecular cues. This finding stemmed from analysis of cell-to-cell variability and computational modeling of time integration between signaling and transcriptional responses. Ultimately, such quantitative approaches challenge the oft-assumed time separation of “fast” signal transduction followed by “slow” gene expression, and they provide a better understanding of complex biological regulation over long time scales.

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