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Wiley, BioEssays, 4(37), p. 452-462, 2015

DOI: 10.1002/bies.201400113

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Sources of dynamic variability in NF-κB signal transduction: A mechanistic model

Journal article published in 2015 by Janina Mothes, Dorothea Busse, Bente Kofahl, Jana Wolf ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The transcription factor NF-κB (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF-κB signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF-κB. By applying mathematical modelling and bifurcation analyses, we show that NF-κB is capable of exhibiting different types of dynamics in response to the same stimulus. We identified the total NF-κB concentration and the IκBα transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF-κB. Both parameters might vary as a result of cell-to-cell variability. The regulation of the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-κB dynamics by crosstalk.