Research ArticleSystems Biology

NF-κB responds to absolute differences in cytokine concentrations

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Science Signaling  19 Jan 2021:
Vol. 14, Issue 666, eaaz4382
DOI: 10.1126/scisignal.aaz4382

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The NF-κB differentiator circuit

Cytokine concentrations fluctuate in a dynamic manner. Son et al. found that the activity of the NF-κB signaling pathway correlated with the rate of change in the concentrations of the cytokines TNF and IL-1β rather than with absolute cytokine concentrations. This behavior, which corresponds to a differentiator circuit in engineering systems, required negative feedback provided by the regulatory proteins A20 and IκBα to encode cellular memory about prior exposures and enabled distinct transcriptional responses to different patterns of cytokine dynamics. Thus, the behavior of the NF-κB pathway as a differentiator circuit ensures the generation of appropriate responses to complex variations in cytokine concentration dynamics.

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