A simple model of NF-κB dynamics reproduces experimental observations.
The mathematical modeling of the NF-κB oscillations has attracted considerable attention in recent times, but there is a lack of simple models in the literature that can capture the main features of the dynamics of this important transcription factor. For this reason we propose a simple model that summarizes the key steps of the NF-κB pathway. We show that the resulting 5-dimensional dynamical system can reproduce different phenomena observed in experiments. Our model can display smooth and spiky oscillations in the amount of nuclear NF-κB and can reproduce the variety of dynamics observed when different stimulations such as TNF-α and LPS are used. Furthermore we show that the model can be easily extended to reproduce the expression of early, intermediate and late genes upon stimulation. As a final example we show that our simple model can mimic the different transcriptional outputs observed when cells are treated with two different drugs leading to nuclear localization of NF-κB: Leptomycin B and Cycloheximide.
San Raffaele University and Scientific Institute, Division of Genetics and Cell Biology, Via Olgettina 58, 20132 Milan, Italy. Electronic address: samuel.zambrano@gmail.com.
Samuel
S
Zambrano
San Raffaele University and Scientific Institute, Division of Genetics and Cell Biology, Via Olgettina 58, 20132 Milan, Italy.
Marco E
ME
Bianchi
San Raffaele University and Scientific Institute, Division of Genetics and Cell Biology, Via Olgettina 58, 20132 Milan, Italy.
Alessandra
A
Agresti
D008962:Models, Theoretical; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic
D016328:NF-kappa B
Mathematical modeling; Oscillations; Signalling pathways; Transcription factor dynamics