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Functional regulation of Slug / Snail2 is dependent on GSK‐3β‐mediated phosphorylation
Author(s) -
Kim Jin Young,
Kim Young Mee,
Yang Chang Hee,
Cho Somi K.,
Lee Jung Weon,
Cho Moonjae
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08674.x
Subject(s) - slug , phosphorylation , cadherin , gsk3b , epithelial–mesenchymal transition , gsk 3 , microbiology and biotechnology , vimentin , phosphorylation cascade , transcription factor , biology , cancer research , gene , transition (genetics) , protein phosphorylation , cell , genetics , protein kinase a , immunology , immunohistochemistry
Snail family proteins regulate transcription of molecules for cell–cell adhesion during epithelial–mesenchymal transition (EMT). Based on putative glycogen synthase kinase 3β (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 with 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.