Redox regulation of the tumor suppressor PTEN by glutathione

Yujeong Kim, Yong Bhum Song, Tae Youl Kim, Inyoung Kim, Seong Jeong Han, Younghee Ahn, Seung Hyun Cho, Cheol Yong Choi, Kee Oh Chay, Sung Yeul Yang, Bong Whan Ahn, Won Ki Huh, Seung Rock Lee

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)3550-3556
Number of pages7
JournalFEBS Letters
Volume584
Issue number16
DOIs
StatePublished - Aug 2010

Keywords

  • Glutathione
  • Hydrogen peroxide
  • PTEN
  • Reactive oxygen species

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