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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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The complexity of p53-mediated metabolic regulation in tumor suppression

Yanqing Liu1, Wei Gu2

  • 1Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, 1130 Nicholas Ave, New York, NY, 10032, USA.

Seminars in Cancer Biology
|March 31, 2021
PubMed

Insights

The tumor suppressor p53 regulates metabolism to prevent cancer. This review details how p53 controls glucose, lipid, amino acid, and iron metabolism, impacting cell death and survival pathways in tumor development.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Metabolic Regulation

Background:

  • The tumor suppressor p53 is a critical barrier against cancer, traditionally known for inducing cell-cycle arrest, senescence, and apoptosis.
  • Emerging evidence indicates p53's tumor suppressive functions extend beyond its classic roles, significantly involving metabolic regulation.
  • Cancer cells exhibit altered metabolism, often the Warburg effect, to support rapid proliferation, a process p53 actively counteracts.

Purpose of the Study:

  • To comprehensively review the multifaceted roles of p53 in regulating diverse metabolic pathways relevant to tumor suppression.
  • To elucidate the mechanisms through which p53 influences glucose, lipid, amino acid, nucleotide, and iron metabolism.
  • To discuss p53's involvement in reactive oxygen species (ROS) production and its impact on ferroptosis, AKT/mTOR signaling, and autophagy.

Main Methods:

  • This review synthesizes findings from numerous published studies.
  • It analyzes the downstream targets of p53 involved in metabolic control.
  • The review integrates knowledge on p53's regulation of key cellular processes like oxidative phosphorylation, glycolysis, and cell death pathways.

Main Results:

  • p53 suppresses glycolysis and promotes mitochondrial oxidative phosphorylation, directly opposing the Warburg effect.
  • p53 regulates multiple metabolic pathways, including glucose, lipid, amino acid, nucleotide, and iron metabolism.
  • p53's metabolic control is complex, influencing both pro-oxidant and antioxidant gene expression, and impacting ferroptosis, AKT/mTOR signaling, and autophagy.

Conclusions:

  • p53's tumor suppressive activity is significantly mediated through intricate regulation of cellular metabolism.
  • Understanding p53-metabolic interactions is crucial for deciphering its complete role in cancer development.
  • The complex interplay between p53, metabolism, and cell fate pathways offers potential therapeutic targets for cancer intervention.
Keywords:
FerroptosisMetabolismTranscriptional activationTumor suppressionp53

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