Abstract
The Tumor Necrosis Factor-α (TNF-α), a cytokine produced during the innate immune response to invading pathogens, is involved in numerous fundamental cellular processes. Here, to understand the temporal activation profiles of the TNF-α regulated signaling network, we developed a dynamic computational model based on the perturbation-response approach and the law of information (signaling flux) conservation. Our simulations show that the temporal average population response of the TNF-α stimulated transcription factors NF-κB and AP-1, and 3 groups of 180 downstream gene expressions follow first-order equations. Using the model, in contrast to a well-known previous study, our model suggests that the continuous activation of the third group of genes is not mainly due to the poor rate of mRNA decay process, rather, the law of signaling flux conservation stipulates the presence of secondary signaling, such as feedback mechanism or autocrine signaling, is crucial. Although the living system is perceived as sophisticated and complex, notably, our work reveals the presence of simple governing principles in cell population dynamics.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hayashi, K., Piras, V., Tomita, M. et al. Emergence of macroscopic simplicity from the Tumor Necrosis Factor-alpha signaling dynamics. Nat Prec (2011). https://doi.org/10.1038/npre.2011.6495.1
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/npre.2011.6495.1
Keywords
This article is cited by
-
Enhancing apoptosis in TRAIL-resistant cancer cells using fundamental response rules
Scientific Reports (2011)