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Review
. 2010 Sep;31(9):1208-12.
doi: 10.1038/aps.2010.151. Epub 2010 Aug 23.

The role of p53 in cell metabolism

Xing-ding Zhang  1 , Zheng-hong Qin, Jin Wang
Affiliations
Review

The role of p53 in cell metabolism

Xing-ding Zhang et al. Acta Pharmacol Sin. 2010 Sep.

Abstract

The p53 tumor suppressor gene has recently been shown to mediate metabolic changes in cells under physiological and pathological conditions. It has been revealed that p53 regulates energy metabolism, oxidative stress, and amino acid metabolism through balancing glycolysis and oxidative phosphorylation (OXPHOS) as well as the autophagy pathway. p53 is activated by metabolic stress through AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) signaling pathways. p53 regulates OXPHOS through the transcriptional regulation of fructose-2,6-bisphosophatase, TP53-induced glycolysis regulator (TIGAR) and synthesis of cytochrome c oxidase (SCO2) subunit of complex IV of the electron transport chain. p53 also indirectly influences the energy metabolism through regulating glucose transporter (GLUT) expression, glutaminase 2 (GLS2) and fatty acid synthase (FAS). In addition, p53 regulates autophagy to provide cell metabolites for surviving through damage regulated autophagy modulator (DRAM1). Here we review the recent findings to elucidate the important role of p53 in cell metabolism.

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Figures

Figure 1
Figure 1
The AMPK-p53-mTOR pathway in metabolic adaptation. Activation of p53 by metabolic stress is regulated by AMP-activated protein kinase (AMPK)-dependent phosphorylation and influenced by mammalian target of rapamycin complex1 (mTORC1). p53 further induces AMPK (both directly and indirectly through the sestrins) and activates the expression of tuberous sclerosis complex 2 (TSC2), resulting in the inhibition of mTOR. The activation of p53 may also cause up-regulation of carnitine palmitoyltransferase (CPT1) and enhancement of β-oxidation of fatty acids. p53 regulates expression of damage-regulated autophagy modulator 1 (DRAM1), which in turn induces autophagy. p53 up-regulates guanidinoacetate methyltransferase (GAMT), which regulates the creatine metabolic pathway involved in fatty acid metabolism.
Figure 2
Figure 2
p53 regulation of energy metabolism. p53 regulates energy metabolism through target proteins that is directly or indirectly involved in energy metabolic pathways. p53 inhibits the expression of the glucose transporters GLUT1 and GLUT4, resulting decrease of the levels of phosphoglycerate mutase (PGM), an enzyme in glycolytic pathway, while increase the expression of TP53-induced glycolysis and apoptosis regulator (TIGAR). TIGAR diverts glucose to an alternative pathway, the pentose phosphate pathway (PPP), which leads to the production of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is used for the removal of reactive oxygenspecies (ROS). Mutant p53 has been found to activate expression of hexokinase 2 (HK2), which is an important enzyme involving in glycolysis. p53 induces GLS2 to enhance mitochondrial respiration by increasing the production of glutamate and α-ketoglutarate. p53 targets another gene named synthesis of cytochrome c oxidase 2 (SCO2). SCO2 regulates the cytochrome c oxidase complex, which is essential for mitochondrial respiration and utilization of oxygen to produce energy (ATP). The end-product of glycolysis, pyruvate, enters the tricarboxylic acid (TCA) cycle located within the mitochondria.
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References

    1. Levine A. p53, the cellular gatekeeper for growth and division. Cell. 1997;88:323–31. - PubMed
    1. Vogelstein B, Lane D, Levine A. Surfing the p53 network. Nature. 2000;408:307–10. - PubMed
    1. Gottlieb E, Vousden KH. p53 Regulation of metabolic pathways. Cold Spring Harb Perspect Biol. 2010;2:a001040. - PMC - PubMed
    1. Hardie DG. The AMP-activated protein kinase pathway — new players upstream and downstream. J Cell Sci. 2004;117:5479–87. - PubMed
    1. Inoki K, Zhu T, Guan K. TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003;115:577–90. - PubMed