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. 2018 May 4;9(34):23780–23823. doi: 10.18632/oncotarget.25267

Figure 6. Mechanism of action of p53 inducers.

Figure 6

Ionizing radiation (IR) induces p53, which increases ROS levels and induces apoptosis. TIGAR and NRF2 may prevent this activity. p53 induction by IR may also induce CXCR2, which induces phosphorylation of p38MAPK and senescence. Genotoxic drugs may have their activities modulated by NRF2, GSH, MDR1, JARID1B and the AKT/mTOR pathway, which is induced by IGF1R. Low drug concentration induces transient p53 expression and the target genes: p21, cyclin D1 and GADD45 that directs the cell to senescence, which can be inhibited by HSP90. Prolonged p53 expression induced by genotoxic drugs is involved in upregulation of E2F1, and the pro-apoptotic genes: TNFRSF10b (Killer-Dr5), TNFRSF6 (Fas-Apo) and PUMA.