Redox signalling and transition metals in the control of the p53 pathway

Biochem Pharmacol. 2000 Jan 1;59(1):25-33. doi: 10.1016/s0006-2952(99)00297-x.


The p53 tumour suppressor protein exerts multiple, antiproliferative effects in response to genotoxic exposures. Reactive oxygen intermediates (ROI) play several distinct roles in the p53 pathway. First, they are important activators of p53 through their capacity to induce DNA strand breaks. Second, they regulate the DNA-binding activity of p53 by modulating the redox status of a critical set of cysteines in the DNA-binding domain, which are also involved in the coordination of zinc. Third, they play a role in the signalling pathways regulated by p53, as several genes encoding redox effectors are transcriptionally controlled by p53. In this review, we summarize the evidence for the involvement of ROI at these three levels. Emphasis is placed on the role of metals and ROI as potential regulators of p53 protein conformation and functions, and on the putative toxicological consequences of such a regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cells, Cultured
  • DNA Damage
  • Humans
  • Metals / metabolism*
  • Metals / toxicity
  • Oxidation-Reduction
  • Protein Conformation
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Metals
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53