ΔNp53 and aging

Lin, Shih‐Chieh; Taatjes, Dylan J.

doi:10.18632/aging.100609

Cited by 2 publications

(1 citation statement)

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“…The awareness of the intense metabolic rewiring in cancer has stimulated research to unravel its origin and regulation. Recent work has also demonstrated that the p53 family plays an important role in regulating metabolism in different settings [ 59 , 61 , 63 , 70 , 72 – 76 ] and suggests that metabolic regulation contributes to the vast complexity of the p53 family functions, including cell death [ 77 – 81 ], redox homeostasis [ 82 ], development [ 83 – 87 ], senescence [ 88 – 90 ], aging [ 91 – 94 ] and fertility [ 95 – 97 ]. For this reason, we sought to investigate whether TAp73 regulates metabolism and how this could relate to physiological roles.…”

Section: Discussionmentioning

confidence: 99%

TAp73 promotes anabolism

et al. 2014

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Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

TAp73 promotes anabolism

et al. 2014

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TAp73 promotes anti-senescence-anabolism not proliferation

Agostini

Niklison-Chirou

Catani

et al. 2014

Aging

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TAp73, a member of the p53 family, has been traditionally considered a tumor suppressor gene, but a recent report has claimed that it can promote cellular proliferation. This assumption is based on biochemical evidence of activation of anabolic metabolism, with enhanced pentose phosphate shunt (PPP) and nucleotide biosynthesis. Here, while we confirm that TAp73 expression enhances anabolism, we also substantiate its role in inhibiting proliferation and promoting cell death. Hence, we would like to propose an alternative interpretation of the accumulating data linking p73 to cellular metabolism: we suggest that TAp73 promotes anabolism to counteract cellular senescence rather than to support proliferation.

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ΔNp53 and aging

Cited by 2 publications

References 8 publications

TAp73 promotes anabolism

TAp73 promotes anabolism

TAp73 promotes anti-senescence-anabolism not proliferation

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