Small C-terminal domain phosphatase enhances snail activity through dephosphorylation

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89 Scopus citations

Abstract

Down-regulation of E-cadherin plays an important role in epithelial-mesenchymal transition (EMT), which is critical in normal development and disease states such as tissue fibrosis and metastasis. Snail, a key transcription repressor of E-cad- herin, is a labile protein with a short half-life and is regulated through phosphorylation, ubiquitination, and degradation. Previously, we showed that GSK-3β phosphorylated two stretches of serine residues within the nuclear export signal and the destruction box of Snail, provoking its cytoplasmic export for ubiquitin-mediated proteasome degradation. However, the mechanism of Snail dephosphorylation and the identity of the Snail-specific phosphatase remain elusive. Using a functional genomic screening, we found that the small C-terminal domain phosphatase (SCP) is a specific phosphatase for Snail. SCP interacted and co-localized with Snail in the nucleus. We also found that SCP expression induced Snail dephosphorylation and stabilization in vitro and in vivo. However, a catalytically inactive mutant of SCP had no effect on Snail. Furthermore, we found that Snail stabilization induced by SCP enhanced snail activity in the suppression of E-cadherin and increased cell migration. Thus, our findings indicate that SCP functions as a Snail phos- phatase to control its phosphorylation and stabilization, and our study provides novel insights for the regulation of Snail during EMT and cancer metastasis.

Original languageEnglish
Pages (from-to)640-648
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number1
DOIs
StatePublished - Jan 2 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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