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. 2011 Apr;2(4):385-91.
doi: 10.1177/1947601911409738.

The Role of p53 in Metabolic Regulation

Anna M Puzio-Kuter  1
Affiliations

The Role of p53 in Metabolic Regulation

Anna M Puzio-Kuter. Genes Cancer. 2011 Apr.

Abstract

The metabolic changes that occur in a cancer cell have been studied for a few decades, but our appreciation of the complexity and importance of those changes is now being realized. The metabolic switch from oxidative phosphorylation to aerobic glycolysis provides intermediates for cell growth and division and is regulated by both oncogenes and tumor suppressor genes. The p53 tumor suppressor gene has long been shown to play key roles in responding to DNA damage, hypoxia, and oncogenic activation. However, now p53 has added the ability to mediate metabolic changes in cells through the regulation of energy metabolism and oxidative stress to its repertoire of activities. It is therefore the focus of this review to discuss the metabolic pathways regulated by p53 and their cooperation in controlling cancer cell metabolism.

Keywords: aerobic glycolysis; oxidative phosphorylation; oxidative stress; p53.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Regulation of metabolism by p53 in proliferating cells. p53 induces TP53-induced glycolysis and apoptosis regulator (TIGAR), hexokinase, inhibits phosphoglycerate mutase (PGM), and represses glucose transporter 1 and 4 (GLUT1 and GLUT4), resulting in inhibition of glycolysis and opposing the Warburg effect that is seen in many cancers. Oxidative phosphorylation is enhanced by p53 induction of synthesis of cytochrome c oxidase 2 (SCO2) and glutaminase 2 (GLS2). p53 can also regulate the glycolytic pathway through IKK/NF-κB signaling.
Figure 2.
Figure 2.
p53 modulates fatty acid metabolism. p53 can regulate fatty acid metabolism through guanidinoacetate N-methyltransferase (GAMT), AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase (CPT-1), and β-oxidation. ACC, acetyl-CoA carboxylase; ACL, ATP citrate lyase; FAS, fatty acid synthase; FAO, fatty acid oxidation; MCD, malonyl-CoA decarboxylase.
Figure 3.
Figure 3.
p53 regulates PI3kinase, Akt, and mTOR pathways to mediate a cell’s adaptation to stress. To do this, p53 regulates the transcription of 4 genes—PTEN, IGF-BP3, TSC2, and AMPK β—which then all negatively regulate Akt kinase and mTOR, leading to a decrease in cell growth. 4EBP1, 4E-binding protein 1; AMPK, AMP-activated protein kinase; IGF-BP3, insulin-like growth factor binding protein 3; IGF1, insulin-like growth factor 1; mTORC, mammalian target of rapamycin complex; PI3K, phosphatidylinositol-3 kinase; PIP3, phosphatidylinositol 3,4,5-trisphosphate; Pten, phosphatase and tensin homologue; Rheb, Ras homolog enriched in brain; S6 kinase, ribosomal protein S6 kinase; Tsc, tuberosclerosis complex.
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References

    1. Warburg O. On respiratory impairment in cancer cells. Science. 1956;124(3215):269-70 - PubMed
    1. Yeung SJ, Pan J, Lee MH. Roles of p53, MYC and HIF-1 in regulating glycolysis: the seventh hallmark of cancer. Cell Mol Life Sci. 2008;65(24):3981-99 - PMC - PubMed
    1. Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer. 2009;9(10):691-700 - PubMed
    1. Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science. 2001;292(5516):504-7 - PubMed
    1. Christofk HR, Vander Heiden MG, Harris MH, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452(7184):230-3 - PubMed

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