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Modelling the Response of FOXO Transcription Factors to Multiple Post-Translational Modifications Made by Ageing-Related Signalling Pathways

Figure 6

The effect of brief and prolonged Akt activity interacting with degradation and acetylation.

Before the start of the time course in the figure, FOXO is pre-equilibrated for 2520 minutes to allow its target gene SOD2 to come into equilibrium, with Akt very weakly active (copy number 100). A–C shows a simulation where acetylation is low (SIRT1 = 103, CBP/P300 = 10), whereas in D–E CBP/P300 is high (SIRT1 = 10, CBP/P300 = 103) so that FOXO is 99% acetylated. As shown by the dosing bars, Akt is activated at t = 360 min for 60 min, and again at t = 540 min for 720 min. The panels show: (A,D): total FOXO and the amount in each compartment, as a fraction of the total at t = 0; (B, E) mRNA in nucleus and cytoplasm for the output gene SOD2; (C,F) SOD2 protein level.

Figure 6

doi: https://doi.org/10.1371/journal.pone.0011092.g006