Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressed in Saccharomyces cerevisiae was reversibly oxidized by hydrogen peroxide and reduced by cellular reductants. Reduction of hPTEN was delayed in each of S. cerevisiae gsh1Delta and gsh2Delta mutants. Expression of gamma-glutamylcysteine synthetase Gsh1 in the gsh1Delta mutant rescued regeneration rate of hPTEN. Oxidized hPTEN was reduced by glutathione in a concentration- and time-dependent manner. Glutathionylated PTEN was detected. Incubation of 293T cells with BSO and knockdown expression of GCLc in HeLa cells by siRNA resulted in the delay of reduction of oxidized PTEN. Also, in HeLa cells transfected with GCLc siRNA, stimulation with epidermal growth factor resulted in the increase of oxidized PTEN and phosphorylation of Akt. These results suggest that the reduction of oxidized hPTEN is mediated by glutathione.
Copyright 2010 Federation of European Biochemical Societies. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Cell Line
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DNA Primers / genetics
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Glutamate-Cysteine Ligase / antagonists & inhibitors
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Glutamate-Cysteine Ligase / genetics
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Glutamate-Cysteine Ligase / metabolism
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Glutathione / metabolism*
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Glutathione Synthase / genetics
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Glutathione Synthase / metabolism
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HeLa Cells
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Humans
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In Vitro Techniques
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Models, Biological
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Mutation
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Oxidation-Reduction
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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RNA, Small Interfering / genetics
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
Substances
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DNA Primers
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RNA, Small Interfering
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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PTEN Phosphohydrolase
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PTEN protein, human
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GSH1 protein, S cerevisiae
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Glutamate-Cysteine Ligase
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Glutathione Synthase
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Glutathione