Sources of dynamic variability in NF-κB signal transduction: a mechanistic model.
Sources of dynamic variability in NF-κB signal transduction: a mechanistic model.
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DOI：
10.1002/bies.201400113
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发表时间：
2015-04
期刊：
影响因子：
4
通讯作者：
Wolf, Jana
中科院分区：
文献类型：
--
作者：
Mothes, Janina;Busse, Dorothea;Kofahl, Bente;Wolf, Jana
关键词：
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.
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