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

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.

SUBMITTER: Mothes J

PROVIDER: S-EPMC4409097 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Mothes Janina J Busse Dorothea D Kofahl Bente B Wolf Jana J

BioEssays : news and reviews in molecular, cellular and developmental biology 20150130 4

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 typ ...[more]

PMID: 25640005

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