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. 2015 Jun 10;6(26):22666–22679. doi: 10.18632/oncotarget.4433

Figure 1. p53 pathway in response to CDDP and Nutlin-3 therapy.

Figure 1

CDDP induces DNA damage by forming DNA cross-links, thereby inducing the activation of ATM/ATR. The latter are able to activate p53 by phosphorylation and the formation of a p53 tetramer, which acts as a transcription factor for among others MDM2 (negative regulation), BAX and PUMA (apoptosis) and p21 (cell cycle arrest). The inhibition of MDM2 by Nutlin-3 results in a high increase in p53 levels in response to CDDP treatment resulting in a synergistic cytotoxic effect.