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Modeling time delay in the NFκB signaling pathway following low dose IL-1 stimulation

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Author(s): Witt Johannes | Barisic Sandra | Sawodny Oliver | Ederer Michael | Kulms Dagmar | Sauter Thomas

Journal: EURASIP Journal on Bioinformatics and Systems Biology
ISSN 1687-4145

Volume: 2011;
Issue: 1;
Start page: 3;
Date: 2011;
Original page

Keywords: IKKbeta | TRAF6 | mathematical model | IL-1 | UVB

ABSTRACT
Abstract Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFκB activation caused by continuous IKKβ phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here, we compare model extensions for low IL-1 doses (0.5 ng/ml), where delayed IKKβ phosphorylation is observed. The extended model including a positive regulatory element, most likely auto-ubiquitination of TRAF6, reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets.

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