Understanding NF‐κB signaling via mathematical modeling
Open Access
- 1 January 2008
- journal article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 4 (1), 192
- https://doi.org/10.1038/msb.2008.30
Abstract
Mammalian inflammatory signaling, for which NF‐κB is a principal transcription factor, is an exquisite example of how cellular signaling pathways can be regulated to produce different yet specific responses to different inflammatory insults. Mathematical models, tightly linked to experiment, have been instrumental in unraveling the forms of regulation in NF‐κB signaling and their underlying molecular mechanisms. Our initial model of the IκB–NF‐κB signaling module highlighted the role of negative feedback in the control of NF‐κB temporal dynamics and gene expression. Subsequent studies sparked by this work have helped to characterize additional feedback loops, the input–output behavior of the module, crosstalk between multiple NF‐κB‐activating pathways, and NF‐κB oscillations. We anticipate that computational techniques will enable further progress in the NF‐κB field, and the signal transduction field in general, and we discuss potential upcoming developments.Keywords
This publication has 59 references indexed in Scilit:
- UV as an Amplifier Rather Than Inducer of NF-κB ActivityMolecular Cell, 2008
- Identification of a Ligand-induced Transient Refractory Period in Nuclear Factor-κB SignalingPublished by Elsevier BV ,2008
- Shared Principles in NF-κB SignalingCell, 2008
- Single TNFα trimers mediating NF-κ B activation: stochastic robustness of NF-κ B signalingBMC Bioinformatics, 2007
- A Fourth IκB Protein within the NF-κB Signaling ModuleCell, 2007
- A homeostatic model of IκB metabolism to control constitutive NF‐κB activityMolecular Systems Biology, 2007
- Minimal model of spiky oscillations in NF-κB signalingProceedings of the National Academy of Sciences of the United States of America, 2006
- IκBε provides negative feedback to control NF-κB oscillations, signaling dynamics, and inflammatory gene expressionThe Journal of cell biology, 2006
- De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signallingNature, 2004
- Activators and target genes of Rel/NF-κB transcription factorsOncogene, 1999