Dual regulation of Snail by GSK-3 -mediated phosphorylation in control of epithelial–mesenchymal transition Binhua P. Zhou1 et al., Nature Cell Biology,

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Dual regulation of Snail by GSK-3 -mediated phosphorylation in control of epithelial–mesenchymal transition Binhua P. Zhou1 et al., Nature Cell Biology, 2004

P Snail GSK3-β P proteasome ?

III Snail GSK3-β ?

Myc- IP:Flag- I -MycIP: Myc + r-P 32 ATP GST-snail Snail GSK3-β P P

Stability Half-lives Snail P P P P P P

P P P P P

MCF7 Snail (-) Snail

P P P

Biochim Biophys Acta ① ②

EGF,IGF Akt, MAPK GSK -3β Snail E-cad EGF,IGF Akt, MAPK GSK -3β Snail E-cad X X X P P

EGF,IGF Akt, MAPK GSK -3β Snail E-cad X X P EGF,IGF Akt, MAPK GSK -3β Snail E-cad X P

* Wnt-dependent regulation of the E-cadherin repressor snail (JBC,2005) : Snail displays ß-catenin-like canonical motifs that support its GSK3ß-dependent phosphorylation, ß-TrCP-directed ubiquitination and proteasomal degradation. : Wnt signaling inhibits Snail phosphorylation and consequently increases Snail protein levels and activity, while driving an in vivo epithelial-mesenchymal transition that is suppressed following Snail knockdown.