Functional regulation of Slug/Snail2 is dependent on GSK-3β-mediated phosphorylation.
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.
Department of Biochemistry, School of Medicine, Jeju National University, South Korea.
Jin Young
JY
Kim
Young Mee
YM
Kim
Chang Hee
CH
Yang
Somi K
SK
Cho
Jung Weon
JW
Lee
Moonjae
M
Cho
D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3