TY - JOUR
AU - Hung, Mien-Chie
AB - The phenotypic changes of increased motility and invasiveness of cancer cells are reminiscent of the epithelial–mesenchymal transition (EMT) that occurs during embryonic development. Snail, a zinc-finger transcription factor, triggers this process by repressing E-cadherin expression; however, the mechanisms that regulate Snail remain elusive. Here we find that Snail is highly unstable, with a short half-life about 25 min. We show that GSK-3β binds to and phosphorylates Snail at two consensus motifs to dually regulate the function of this protein. Phosphorylation of the first motif regulates its β-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. Furthermore, inhibition of GSK-3β results in the upregulation of Snail and downregulation of E-cadherin in vivo. Thus, Snail and GSK-3β together function as a molecular switch for many signalling pathways that lead to EMT.
TI - Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial–mesenchymal transition
JF - Nature Cell Biology
DO - 10.1038/ncb1173
DA - 2004-09-26
UR - https://www.deepdyve.com/lp/springer-journals/dual-regulation-of-snail-by-gsk-3-mediated-phosphorylation-in-control-hdW3sg7oM5
SP - 931
EP - 940
VL - 6
IS - 10
DP - DeepDyve
ER -