FEBS J. 2012 Jun 22. doi: 10.1111/j.1742-4658.2012.08674.x. [Epub ahead of print]
Functional regulation of Slug/Snail2 is dependent on GSK-3β-mediated phosphorylation.
Source
Department of Biochemistry, School of Medicine Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 690-756 Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea Institute of Medical Science, Jeju National University, Jeju 690-756.
Abstract
Snail family proteins regulate transcription of molecules for cell-cell adhesion during epithelial-mesenchymal transition (EMT). Based on putative GSK-3β phosphorylation sites within the Slug/Snail2, we explored the significance of GSK-3β-mediated phosphorylation in Slug/Snail2 expression during EMT. Mutation of the putative GSK-3β phosphorylation sites (S92/96A or S100/104A) enhanced the Slug/Snail2-mediated EMT properties of E-cadherin repression and vimentin induction, compared to wild-type Slug/Snail2. S92/96A mutation inhibited degradation of Slug/Snail2 and S100/104A mutation extended nuclear stabilization. Inhibition of GSK-3β activity caused similar effects, as did the phosphorylation mutations. Thus, our study suggests that GSK-3β-mediated phosphorylation of Slug/Snail2 controls its turnover and localization during EMT.
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