Figure 1.

Reciprocal regulation between p53 and malic enzymes. p53 directly represses transcription of ME1 and ME2, which encode enzymes catalyzing the conversion of malate to pyruvate, with concomitant generation of NADPH. NADPH is essential for anabolic metabolism and cellular antioxidant function, both of which are implicated in tumor promotion. Suppression of ME1 or ME2 expression induces p53 activation, cellular senescence and tumor suppression through MDM2 and ROS/AMPK pathways, respectively.