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Comparative Study
. 2003 Nov;13(11):2413-22.
doi: 10.1101/gr.1195703. Epub 2003 Oct 14.

Investigations into the analysis and modeling of the TNF alpha-mediated NF-kappa B-signaling pathway

Kwang-Hyun Cho  1 , Sung-Young Shin, Hyeon-Woo Lee, Olaf Wolkenhauer
Affiliations
Comparative Study

Investigations into the analysis and modeling of the TNF alpha-mediated NF-kappa B-signaling pathway

Kwang-Hyun Cho et al. Genome Res. 2003 Nov.

Abstract

In this study, we propose a system-theoretic approach to the analysis and quantitative modeling of the TNFalpha-mediated NF-kappaB-signaling pathway. Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, in the control of cell proliferation, differentiation, and apoptosis. To date, there have been numerous approaches to model cellular dynamics. The most prominent uses ordinary differential equations (ODEs) to describe biochemical reactions. This approach can provide us with mathematically well-founded and tractable interpretations regarding pathways, especially those best described by enzyme reactions. This work first introduces a graphical method to intuitively represent the TNFalpha-mediated NF-kappaB-signaling pathway and then utilizes ODEs to quantitatively model the pathway. The simulation study shows qualitative validation of the proposed model compared with experimental results for this pathway. The proposed system-theoretic approach is expected to be further applicable to predict the signaling behavior of NF-kappaB in a quantitative manner for any variation of the ligand, TNFalpha.

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Figures

Figure 1
Figure 1
Reaction profile of the basic enzyme kinetics.
Figure 2
Figure 2
Graphical representation of the reaction kinetics.
Figure 3
Figure 3
The complemented graphical model of an enzyme.
Figure 4
Figure 4
Graphical representation of the complemented model of the reaction kinetics.
Figure 5
Figure 5
Simulation results of the complemented reaction kinetics.
Figure 6
Figure 6
Graphical model of the TNFα-mediated NF-κB-signaling pathway.
Figure 7
Figure 7
Binding of TNFα to TNFR1.
Figure 8
Figure 8
Recruitment of TRADD.
Figure 9
Figure 9
Recruitment of RIP.
Figure 10
Figure 10
Recruitment of TRAF2.
Figure 11
Figure 11
Activation of IKK.
Figure 12
Figure 12
Activation of NF-κB.
Figure 13
Figure 13
TNFα.
Figure 14
Figure 14
TNFR1.
Figure 15
Figure 15
TNFR1 complex.
Figure 16
Figure 16
TRADD.
Figure 17
Figure 17
TRADD complex.
Figure 18
Figure 18
RIP.
Figure 19
Figure 19
RIP complex.
Figure 20
Figure 20
TRAF2.
Figure 21
Figure 21
TRAF2 complex.
Figure 22
Figure 22
IKK complex.
Figure 23
Figure 23
Activated IKK.
Figure 24
Figure 24
NFκB/IkB.
Figure 25
Figure 25
IκB complex.
Figure 26
Figure 26
Phosphorylated IκB.
Figure 27
Figure 27
NFκB.
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References

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