title: 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.
authors: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Janina
authors: J
authors: Mothes
authors: Dorothea
authors: D
authors: Busse
authors: Bente
authors: B
authors: Kofahl
authors: Jana
authors: J
authors: Wolf
mesh_terms: D002470:Cell Survival / Q000502:physiology; D020672:I-kappa B Proteins / Q000378:metabolism; D008962:Models, Theoretical; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha
keywords: IκBα transcription; bifurcation analysis; cell-to-cell variability; fold change; mathematical model; oscillations; steady state
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