Figure 1. P53 regulates critical points in cell signaling and metabolism.

p53 is involved in different critical points of metabolism control and cell signaling, being able to regulate key proteins and enzymes in cellular response to cancer. The Figure shows how p53 suppresses glycolysis and increases OxPhos (oxidative phosphorylation) while it regulates IGF signaling pathway. p53 regulates glucose uptake by some glucose transporters (GLUT1, GLUT3 and GLUT4) and regulates direct and indirectly enzymes in its downstream oxidation to pyruvate – HK, TIGAR, PFK1/2, G6PDH, PGM and ME1. p53 is also important for mitochondrial respiration through regulation of MCD, LPIN1, PANK1, CPT1C and SCO2. Furthermore, p53 regulates enzymes involved in amino acids metabolism such as PHGDH, which participates in serine metabolism derived from the 3PG, and GLS2, which catalyzes the hydrolysis of glutamine to glutamate, increasing TCA cycle flux. In cell signaling transduction, p53 reveals a crucial activity in suppressing downstream proteins of the IGF pathway, such as AKT, AMPK and S6Ks, modulating processes such as cell growth, autophagy and lipid metabolism. In cell signaling, proteins with positive relation with cancer are shown in red and negative relation in blue. Regular arrows represent activation and blunt arrows inhibition. Thicker arrows indicate increased reactions in cancer when compared to thin arrows.