Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster

Zuohe Song, Negin Saghafi, Vijay Gokhale, Marc Brabant, Emmanuelle Meuillet

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Human Thioredoxin-1 (hTrx-1) is a small redox protein with a molecular weight of 12 kDa that contains two cysteine residues found in its catalytic site. HTrx-1 plays an important role in cell growth, apoptosis, and cancer patient prognosis. Recently, we have demonstrated that hTrx-1 binds to the C2 domain of the human tumor suppressor, PTEN, in a redox dependent manner. This binding leads to the inhibition of PTEN lipid phosphatase activity in mammalian tissue culture systems. In this study, we show that over-expression of hTrx-1 in Drosophila melanogaster promotes cell growth and proliferation during eye development as measured by eye size and ommatidia size. Furthermore, hTrx-1 rescues the small eye phenotype induced by the over-expression of PTEN. We demonstrate that this rescue of the PTEN-induced eye size phenotype requires cysteine-218 in the C2 domain of PTEN. We also show that hTrx-1 over-expression results in increased Akt phosphorylation in fly head extracts supporting our observations that the hTrx-1-induced eye size increase results from the inhibition of PTEN activity. Our study confirms the redox regulation of PTEN through disulfide bond formation with the hTrx-1 in Drosophila and suggests conserved mechanisms for thioredoxins and their interactions with the phosphatidylinositol-3-kinase signaling pathway in humans and fruit flies.

Original languageEnglish (US)
Pages (from-to)1161-1171
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number6
DOIs
Publication statusPublished - Apr 1 2007

    Fingerprint

Keywords

  • Akt
  • Drosophila
  • Eye development
  • PTEN
  • Thioredoxin

ASJC Scopus subject areas

  • Cell Biology

Cite this