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Redox regulation of the tumor suppressor PTEN by glutathione

  作者 Kim, Y; Song, YB; Kim, TY; Kim, I; Han, SJ; Ahn, Y; Cho, SH; Choi, CY; Chay, KO; Yang, SY; Ahn, BW; Huh, WK; Lee, SR  
  选自 期刊  FEBS Letters;  卷期  2010年584-16;  页码  3550-3556  
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[摘要]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 gsh1 Delta and gsh2 Delta mutants. Expression of gamma-glutamylcysteine synthetase Gsh1 in the gsh1 Delta 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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

 
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