Small C-terminal domain phosphatase enhances snail activity through dephosphorylation. Wu, Y., Evers, B. M., & Zhou, B. P. The Journal of Biological Chemistry, 284(1):640–648, January, 2009. doi abstract bibtex 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-cadherin, is a labile protein with a short half-life and is regulated through phosphorylation, ubiquitination, and degradation. Previously, we showed that GSK-3beta 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 phosphatase to control its phosphorylation and stabilization, and our study provides novel insights for the regulation of Snail during EMT and cancer metastasis.
@article{wu_small_2009,
title = {Small {C}-terminal domain phosphatase enhances snail activity through dephosphorylation},
volume = {284},
issn = {0021-9258},
doi = {10.1074/jbc.M806916200},
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-cadherin, is a labile protein with a short half-life and is regulated through phosphorylation, ubiquitination, and degradation. Previously, we showed that GSK-3beta 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 phosphatase to control its phosphorylation and stabilization, and our study provides novel insights for the regulation of Snail during EMT and cancer metastasis.},
language = {eng},
number = {1},
journal = {The Journal of Biological Chemistry},
author = {Wu, Yadi and Evers, B. Mark and Zhou, Binhua P.},
month = jan,
year = {2009},
pmid = {19004823},
pmcid = {PMC2610500},
keywords = {Active Transport, Cell Nucleus, Cadherins, Cell Movement, Cell Nucleus, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, HeLa Cells, Humans, Neoplasm Metastasis, Neoplasms, Nuclear Export Signals, Phosphoprotein Phosphatases, Phosphorylation, Proteasome Endopeptidase Complex, Repressor Proteins, Snail Family Transcription Factors, Substrate Specificity, Transcription Factors, Ubiquitin},
pages = {640--648},
}
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Previously, we showed that GSK-3beta 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 phosphatase to control its phosphorylation and stabilization, and our study provides novel insights for the regulation of Snail during EMT and cancer metastasis.","language":"eng","number":"1","journal":"The Journal of Biological Chemistry","author":[{"propositions":[],"lastnames":["Wu"],"firstnames":["Yadi"],"suffixes":[]},{"propositions":[],"lastnames":["Evers"],"firstnames":["B.","Mark"],"suffixes":[]},{"propositions":[],"lastnames":["Zhou"],"firstnames":["Binhua","P."],"suffixes":[]}],"month":"January","year":"2009","pmid":"19004823","pmcid":"PMC2610500","keywords":"Active Transport, Cell Nucleus, Cadherins, Cell Movement, Cell Nucleus, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, HeLa Cells, Humans, Neoplasm Metastasis, Neoplasms, Nuclear Export Signals, Phosphoprotein Phosphatases, Phosphorylation, Proteasome Endopeptidase Complex, Repressor Proteins, Snail Family Transcription Factors, Substrate Specificity, Transcription Factors, Ubiquitin","pages":"640–648","bibtex":"@article{wu_small_2009,\n\ttitle = {Small {C}-terminal domain phosphatase enhances snail activity through dephosphorylation},\n\tvolume = {284},\n\tissn = {0021-9258},\n\tdoi = {10.1074/jbc.M806916200},\n\tabstract = {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-cadherin, is a labile protein with a short half-life and is regulated through phosphorylation, ubiquitination, and degradation. Previously, we showed that GSK-3beta 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. 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