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Redox regulation of the tumor suppressor PTEN by glutathione |
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| Authors: | Yujeong Kim Yong Bhum Song Tae-Youl Kim Seong-Jeong Han Younghee Ahn Cheol Yong Choi Sung Yeul Yang Won-Ki Huh |
| Institution: | a Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea b School of Biological Sciences, Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University, Seoul 151-747, Republic of Korea c School of Biological Sciences and technology, Chonnam National University, Gwangju 500-757, Republic of Korea d Department of Pediatrics, University of Calgary and Alberta Health Services-Calgary Zone, 2888 Shaganappi Trail, NW Calgary, Alberta, Canada T3B 6A8 e Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA f Department of Biological Sciences, Sungkyunkwan University, 300 Chunchundong, Suwon 440-746, Republic of Korea |
| 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 gsh1Δ and gsh2Δ mutants. Expression of γ-glutamylcysteine synthetase Gsh1 in the gsh1Δ 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. |
| Keywords: | PTEN phosphatase and tensin homolog deleted on chromosome 10 H2O2 hydrogen peroxide GSH glutathione Trx thioredoxin Gsh1 γ-glutamylcysteine synthetase Gsh2 GSH synthetase NEM N-ethylmaleimide PAGE polyacrylamide gel electrophoresis HPLC high-performance liquid chromatography DTT dithiothreitol BSO buthionine sulfoximine EGF epidermal growth factor Glu glutamate Cys cysteine |
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