Selenomethionine regulation of p53 by a ref1-dependent redox mechanism

Young R. Seo, Mark Kelley, Martin L. Smith

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

The cancer chemopreventive properties of selenium compounds are well documented, yet little is known of the mechanism(s) by which these agents inhibit carcinogenesis. We show that selenium in the form of selenomethionine (SeMet) can activate the p53 tumor suppressor protein by a redox mechanism that requires the redox factor Ref1. Assays to measure direct reduction/oxidation of p53 showed a SeMet-dependent response that was blocked by a dominant-negative Ref1. By using a peptide containing only p53 cysteine residues 275 and 277, we demonstrate the importance of these residues in the SeMet-induced response. SeMet induced sequence-specific DNA binding and transactivation by p53. Finally, cellular responses to SeMet were determined in mouse embryo fibroblasts wild-type or null for p53 genes. The evidence suggests that the DNA repair branch of the p53 pathway was activated. The central relevance of DNA repair to cancer prevention is discussed.

Original languageEnglish
Pages (from-to)14548-14553
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number22
DOIs
StatePublished - Oct 29 2002

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Selenomethionine
Oxidation-Reduction
DNA Repair
Selenium Compounds
Tumor Suppressor Protein p53
p53 Genes
Selenium
Transcriptional Activation
Cysteine
Neoplasms
Carcinogenesis
Embryonic Structures
Fibroblasts
Peptides

Keywords

  • APE/Ref1
  • Cancer chemoprevention
  • DNA repair
  • P53 tumor suppressor gene
  • Selenium

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. / Seo, Young R.; Kelley, Mark; Smith, Martin L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 22, 29.10.2002, p. 14548-14553.

Research output: Contribution to journalArticle

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