Redox regulation of the tumor suppressor PTEN by glutaredoxin 5 and Ycp4

Biochem Biophys Res Commun. 2011 Apr 1;407(1):175-80. doi: 10.1016/j.bbrc.2011.02.133. Epub 2011 Mar 1.

Abstract

Human PTEN (phosphatase and tensin homolog deleted on chromosome 10; a phosphatidylinositol 3-phosphatase) expressed in Saccharomyces cerevisiae was oxidized in a time- and H(2)O(2)-concentration-dependent manner. Oxidized hPTEN was reduced by cellular reductants as in human cells. The reduction rate of oxidized hPTEN was monitored in S. cerevisiae mutants in which the genes involved in redox homeostasis had been disrupted. Reduction of hPTEN was delayed in each of S. cerevisiae grx5Δ and ycp4Δ mutants. Expression of Grx5 and Ycp4 in each of the mutants rescued the reduction rate of oxidized hPTEN. Furthermore, an in vitro assay revealed that the human Grx5/GSH system efficiently catalyzed the reduction of oxidized hPTEN. These results suggest that the reduction of oxidized hPTEN is regulated by Grx5 and Ycp4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Flavodoxin / metabolism*
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Molecular Sequence Data
  • Oxidation-Reduction
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Flavodoxin
  • Glutaredoxins
  • Saccharomyces cerevisiae Proteins
  • YCP4 protein, S cerevisiae
  • Hydrogen Peroxide
  • PTEN Phosphohydrolase
  • PTEN protein, human