Tumor suppressor p53 and its mutants in cancer metabolism

Cancer Lett. 2015 Jan 28;356(2 Pt A):197-203. doi: 10.1016/j.canlet.2013.12.025. Epub 2013 Dec 24.


Tumor-suppressor p53 plays a key role in tumor prevention. As a transcription factor, p53 transcriptionally regulates its target genes to initiate different biological processes in response to stress, including apoptosis, cell cycle arrest or senescence, to exert its function in tumor suppression. Recent studies have revealed that metabolic regulation is a novel function of p53. Metabolic changes have been regarded as a hallmark of tumors and a key contributor to tumor development. p53 regulates many different aspects of metabolism, including glycolysis, mitochondrial oxidative phosphorylation, pentose phosphate pathway, fatty acid synthesis and oxidation, to maintain the homeostasis of cellular metabolism, which contributes to the role of p53 in tumor suppression. p53 is frequently mutated in human tumors. In addition to loss of tumor suppressive function, tumor-associated mutant p53 proteins often gain new tumorigenic activities, termed gain-of-function of mutant p53. Recent studies have shown that mutant p53 mediates metabolic changes in tumors as a novel gain-of-function to promote tumor development. Here we review the functions and mechanisms of wild-type and mutant p53 in metabolic regulation, and discuss their potential roles in tumorigenesis.

Keywords: Metabolism; Mutant p53; Tumor suppressor; p53.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Cellular Senescence / genetics
  • Energy Metabolism / genetics*
  • Fatty Acids / metabolism
  • Glycolysis / genetics
  • Humans
  • Mitochondria / metabolism
  • Mutation
  • Neoplasms / metabolism*
  • Oxidative Phosphorylation
  • Pentose Phosphate Pathway / genetics
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*


  • Fatty Acids
  • Tumor Suppressor Protein p53