title: Redox regulation of the tumor suppressor PTEN by glutathione.
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.
authors.affiliation: 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.
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Kim
authors.forename: Yong Bhum
authors.initials: YB
authors.lastname: Song
authors.forename: Tae-Youl
authors.initials: TY
authors.lastname: Kim
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.forename: Seong-Jeong
authors.initials: SJ
authors.lastname: Han
authors.forename: Younghee
authors.initials: Y
authors.lastname: Ahn
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Cho
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
authors.forename: Kee-Oh
authors.initials: KO
authors.lastname: Chay
authors.forename: Sung Yeul
authors.initials: SY
authors.lastname: Yang
authors.forename: Bong Whan
authors.initials: BW
authors.lastname: Ahn
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Huh
authors.forename: Seung-Rock
authors.initials: SR
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009154:Mutation; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C490862:GSH1 protein, S cerevisiae; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione