→ SNAI1|pho@Nucleus References
PMID:15459715
PMID:15448698
Dual regulation of Snail by GSK3B-mediated phosphorylation in control of EMT.
Snail is highly unstable, with a short half-life about 25 min.
GSK-3b binds to and phosphorylates Snail at two consensus motifs to dually regulate the function of this protein.
Phosphorylation of the first motif regulates its b-Trcp-mediated ubiquitination, whereas phosphorylation of the second motif controls its subcellular localization.
A variant of Snail (Snail-6SA), which abolishes these phosphorylations, is much more stable and resides exclusively in the nucleus to induce EMT
Inhibition of GSK-3b results in the upregulation of Snail and downregulation of E-cadherin in vivo
Thus, the inhibition of GSK-3b by many extracellular pathways suppresses the phosphorylation of Snail and hence induces the nuclear localization and protein stabilization of Snail, which leads to EMT.