p53-dependent regulation of metabolic function through transcriptional activation of pantothenate kinase-1 gene

Wang, Shang–Jui; Yu, Guowu; Jiang, Lei; Li, Tongyuan; Lin, Qing; Tang, Yi; Gu, Wei

doi:10.4161/cc.23597

Cited by 47 publications

(57 citation statements)

References 27 publications

(31 reference statements)

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“…p53 has been reported to both inhibit and activate gluconeogenesis [85][86][87] , and the regulation of glucose levels by p53 is likely to be context and tissue dependent. A recent study showed that p53 suppresses gluconeogenesis by activating the deacetylase sirtuin 6 (SIRT6).…”

Section: Nature Reviews | Molecular Cell Biologymentioning

confidence: 98%

“…LPIN1 translocates to the nucleus under nutrient stress conditions to function as a transcriptional co-activator and regulate the transcription of genes involved in FAO 97 . Pantothenate kinase 1 (PANK1) -which is essential in CoA biosynthesis -is also a p53 target 87 . CoA is crucial for many metabolic processes, including β-oxidation, the main FAO pathway.…”

Section: Nature Reviews | Molecular Cell Biologymentioning

confidence: 99%

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p53 in survival, death and metabolic health: a lifeguard with a licence to kill

Kruiswijk

Labuschagne

Vousden

2015

Nat Rev Mol Cell Biol

915

792

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The function of p53 as a tumour suppressor has been attributed to its ability to promote cell death or permanently inhibit cell proliferation. However, in recent years, it has become clear that p53 can also contribute to cell survival. p53 regulates various metabolic pathways, helping to balance glycolysis and oxidative phosphorylation, limiting the production of reactive oxygen species, and contributing to the ability of cells to adapt to and survive mild metabolic stresses. Although these activities may be integrated into the tumour suppressive functions of p53, deregulation of some elements of the p53-induced response might also provide tumours with a survival advantage.

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Section: Nature Reviews | Molecular Cell Biologymentioning

confidence: 98%

Section: Nature Reviews | Molecular Cell Biologymentioning

confidence: 99%

p53 in survival, death and metabolic health: a lifeguard with a licence to kill

Kruiswijk

Labuschagne

Vousden

2015

Nat Rev Mol Cell Biol

915

792

View full text Add to dashboard Cite

show abstract

“…ChIP-ChIP assays were performed in transfected H1299 cells or A375 cells as described previously (30). The primers used for p53 the ChIP assay were as follows: PHGDH forward, 5Ј-TGAGAATATGCGGTGTTTGG-3Ј; PHGDH reverse, 5Ј-GGGTAAATGTGCAAGGCACT-3Ј; TIGAR forward, 5Ј-CGGCAGGTCTTAGATAGCTT-3Ј; and TIGAR reverse, 5Ј-GGCAGCCGGCATCAAAAACA-3Ј.…”

Section: Methodsmentioning

confidence: 99%

“…M0201S, New England Biolabs) and purified using Bio-Spin 30 columns (Bio-Rad). The protein-DNA binding reactions were performed as described previously (30). In supershift assays, 100 ng of pAb421 (Millipore) antibody was added to the reactions.…”

Section: Methodsmentioning

confidence: 99%

p53 Protein-mediated Regulation of Phosphoglycerate Dehydrogenase (PHGDH) Is Crucial for the Apoptotic Response upon Serine Starvation

Wang

Jiang

et al. 2015

Journal of Biological Chemistry

Self Cite

108

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Background: PHGDH encodes a key metabolic enzyme in the serine biosynthesis pathway and is frequently amplified in melanomas. Results: p53 transcriptionally represses PHGDH expression. Serine starvation promotes p53-mediated apoptosis in melanomas through PHGDH suppression. Conclusion: p53-mediated repression of PHGDH enhances the apoptotic response upon serine starvation in melanoma cells. Significance: The combination of the drugs activating p53 and serine deprivation could be a better treatment for melanomas.

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“…p53 also may impede metabolism by reducing glucose import (4) or by inhibiting the pentose phosphate pathway (PPP) (5). More recently, context-dependent inhibitory (6) or stimulatory (7,8) effects of p53 on gluconeogenesis have been reported. It thus is clear that p53 plays important roles in glucose regulation in mammalian cells.…”

mentioning

confidence: 99%

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

Zhang

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

193

165

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In mammalian cells, tumor suppressor p53 plays critical roles in the regulation of glucose metabolism, including glycolysis and oxidative phosphorylation, but whether and how p53 also regulates gluconeogenesis is less clear. Here, we report that p53 efficiently down-regulates the expression of phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), which encode rate-limiting enzymes in gluconeogenesis. Cell-based assays demonstrate the p53-dependent nuclear exclusion of forkhead box protein O1 (FoxO1), a key transcription factor that mediates activation of PCK1 and G6PC, with consequent alleviation of FoxO1-dependent gluconeogenesis. Further mechanistic studies show that p53 directly activates expression of the NAD + -dependent histone deacetylase sirtuin 6 (SIRT6), whose interaction with FoxO1 leads to FoxO1 deacetylation and export to the cytoplasm. In support of these observations, p53-mediated FoxO1 nuclear exclusion, down-regulation of PCK1 and G6PC expression, and regulation of glucose levels were confirmed in C57BL/J6 mice and in liver-specific Sirt6 conditional knockout mice. Our results provide insights into mechanisms of metabolism-related p53 functions that may be relevant to tumor suppression.

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p53-dependent regulation of metabolic function through transcriptional activation of pantothenate kinase-1 gene

Cited by 47 publications

References 27 publications

p53 in survival, death and metabolic health: a lifeguard with a licence to kill

p53 in survival, death and metabolic health: a lifeguard with a licence to kill

p53 Protein-mediated Regulation of Phosphoglycerate Dehydrogenase (PHGDH) Is Crucial for the Apoptotic Response upon Serine Starvation

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

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