Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster.
Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster.
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DOI：
10.1016/j.yexcr.2007.01.004
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发表时间：
2007-04
影响因子：
3.7
通讯作者：
Zuohe Song;N. Saghafi;V. Gokhale;Marc C. Brabant;E. Meuillet
中科院分区：
文献类型：
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作者：
Zuohe Song;N. Saghafi;V. Gokhale;Marc C. Brabant;E. Meuillet
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.
