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Figure 11 | BMC Systems Biology

Figure 11

From: A mathematical model of the unfolded protein stress response reveals the decision mechanism for recovery, adaptation and apoptosis

Figure 11

Activation of the UPR following the accumulation of UFP in the ER. Synchronised activation of the three receptors, IRE1 α, ATF6 and PERK, is shown in (a). Splicing of the XBP1 mRNA and the displacement of BiP from IRE1 α are shown in (b). Relative timing of translation attenuation and the signal transduction through the PERK branch are plotted in (c). The time axis in (c) for early activation is given in log-scale for improved visual discrimination. The analogous experimental observations as adapted from Figure 8B of DuRose et al. 2006 [23](a), Figure 7C of DuRose et al. 2006 [23](b) and Figure 3A of Marciniak et al. 2004 [53](c) are given in the insets of the figures. The level of phosphorylated receptor is calculated by multiplying the activated IRE1 α and PERK with the stoichiometry of the activated complex. The percentage of cleaved ATF6 is calculated with respect to the amount of ATF6 on the ER membrane and Golgi body together with cleaved ATF6. In order to facilitate the effective comparison of partial and total activation levels of different components, both simulations and data are re-normalised to 0-100% of their respective ranges. As a result, the 50% mark along the y-axis represents the median of the range of values observed from 0 to 100 atu (or 150 atu for (c)) for each component. The parameters used for the simulations are given in Additional file 1: Table S2. The moderate stress condition is chosen with reference to Figure 10. The experimental data presented are extracted from the respective publications with the aim of aiding visual comparison. The reader is referred to these publications for the original reports of the data.

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