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Fig. 3 | BMC Systems Biology

Fig. 3

From: Differentiation resistance through altered retinoblastoma protein function in acute lymphoblastic leukemia: in silico modeling of the deregulations in the G1/S restriction point pathway

Fig. 3

Simulation results of the reference model [40] for 900 min (15 h). Human HCT116 colon carcinoma cells grown under conditions of constant growth factor exposure. (a) The levels of hypo-phosphorylated pRb (hypo-pRb, purple) rapidly rise during the first min of G1 phase, due to phosphorylation of un-phosphorylated pRb species (pRb, grey) by CyclinD:Cdk4,6, and remain steadily high until the activation of the metabolism-related activating modifier switch (at 240 min); this in turn activates Cyclin E:Cdk2 and Cyclin A:Cdk1,2 complexes (Cyclin E:Cdk2 not shown in the figure). As a consequence, the majority of hypo-pRb is transformed to hyper-phosphorylated pRb (hyper-pRb, light purple). (b) In the time interval during which the levels of pRb and hypo-pRb are significant, free E2F transcription factors (E2F, green) are predominantly bound to these versions of pRb (orange). When hyper-pRb starts to dominate the levels of retinoblastoma protein, E2F is liberated and the levels of free transcription factors quickly elevate. (c) Cyclin A levels (red) show steady or even decreasing trends until the activation of the modifier switch. After this activation they gradually rise, due to E2F liberation, reaching the indicative of S-phase passage 300 (molecules/cell) threshold at approximately 600 min (indicated in green). (d) Cyclin D levels (cyan) do not show any significant variation during the execution of the model

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