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

2. P Snail GSK3-β P proteasome ?

3. III Snail GSK3-β ?

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

5. Stability Half-lives Snail P P P P P P

7. P P P P P

9. MCF7 Snail (-) Snail

10. P P P

11. Biochim Biophys Acta. 2004 ① ②

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

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

15. * 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.