PMAIP1 and lymphoma: Myc upregulates p19Arf expression, probably indirectly, and p19Arf binds to and neutralises Mdm2, thereby preventing inhibition and degradation of p53 and facilitating expression of pro-apoptotic p53 targets, BH3-only proteins Puma and Noxa and, in a negative feedback loop, Mdm2.53 Although expression of dnFoxO reduced the selective pressure to inactivate the p19Arf/p53 pathway during lymphomagenesis in Eμ-myc mice,26 this was not the case for FoxO3−/−Eμ-myc lymphomas (Figure 8).