Redox regulation of the tumor suppressor PTEN by glutathione.
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.
Kim
Yujeong
Y
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.
Song
Yong Bhum
YB
Kim
Tae-Youl
TY
Kim
Inyoung
I
Han
Seong-Jeong
SJ
Ahn
Younghee
Y
Cho
Seung-Hyun
SH
Choi
Cheol Yong
CY
Chay
Kee-Oh
KO
Yang
Sung Yeul
SY
Ahn
Bong Whan
BW
Huh
Won-Ki
WK
Lee
Seung-Rock
SR
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
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