Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion

Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion

p53 is a commonly mutated transcription factor in cancer, and is one of the most studied tumour suppressors. Here, the authors elucidate the interaction of p53 with the metabolism, specifically gluconeogenesis: the process by which glucose is built from non-carbohydrate amino acids, which could conceivably be essential for tumour growth. The authors show that p53 directly activates SIRT6, which induced translocation of FOXO1 to the cytoplasm, which activates the enzymes PCK1 and G6PC, which encode the rate-limiting enzymes for gluconeogenesis.