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

Protein-Thiol Oxidation and Cell Death: Regulatory Role of Glutaredoxins

“…This protein modification on human PTEN is normally reversed quickly in yeast; however, when various Grx genes, particularly grx5, are mutated, this reversibility is delayed. These results imply that human PTEN is a substrate for yeast Grx5 (50). It will be important to confirm that PTEN-SSG is a substrate for Grx, and to carry out studies of the glutathionylation status of PTEN and the apoptotic susceptibility of cells in which Grx1 has been knocked down.…”

“…In a recent study, human PTEN was found to be susceptible to reversible protein modification upon treatment with H 2 O 2 (50). This protein modification on human PTEN is normally reversed quickly in yeast; however, when various Grx genes, particularly grx5, are mutated, this reversibility is delayed.…”

The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans

“…Hydrogen peroxide induced oxidation of PTEN has been shown to be reduced by glutathione in yeast and human cells (Kim et al, 2011) while oxidative stress significantly increased levels of GSH in cells from patients with a missense mutation in PINK1 in comparison to controls (Grünewald et al, 2009). When animals with the pink-1 or daf-18 mutations were treated with GSH, they did not respond favorably; none of these animals showed improved percentages of animals moving normally after treatment (Fig.…”

“…6) which had only previously been observed by loss of GLRX-21, the glutaredoxin 2 (GRX)2-like protein (Estevez et al, 2012; Morgan et al, 2010). ROS has been demonstrated to oxidize and thus inactivate PTEN and this process requires both GRX and GSH to be reduced (Kim et al, 2011). Thus, a similar mechanism may occur in C. elegans accounting for the GSH insensitivity phenotype of the daf-18 mutants (Fig.…”

“…1 = Ponugoti et al (2012); Ref. 2 = Kim et al (2011), Loh et al (2009); Ref. 3 = Mei et al (2009); Ref.…”