Figure 3

Cross talk between NF-κB and p53. There are many lines of crosstalk between the p53 and NF-κB pathways. A few of these are highlighted, such as AKT and the transcriptional co-activator proteins CREB-binding protein (CBP) and the related p300 protein. AKT can activate both IκB kinases (IKKs) and phosphorylate p65. AKT-mediated MDM2 phosphorylation can also inhibit p53 stabilization. Due to competition for the limited pool of CBP/p300, this protein also plays a crucial role in determining which pathway dominates in terms of cellular outcome. In addition, NF-κB has been shown to directly upregulate the levels of MDM2 mRNA and hence the protein. One promising aspect of quinacrine is its simultaneous ability to inhibit AKT, to induce the p53 pathway, and to inhibit the NF-κB pathway. Adapted from Dey et al. [279].