C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization

The epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process converting epithelial cells into mesenchymal cell morphology. Snail is a critical regulator of EMT by both suppressing epithelial gene expression and promoting mesenchymal gene expression. Expression and activity of S...

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Main Authors: Yulan Zhao, Jinquan Liu, Fenfang Chen, Xin-Hua Feng
Format: Article
Language:English
Published: The Royal Society 2018-04-01
Series:Open Biology
Subjects:
Online Access:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170274
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author Yulan Zhao
Jinquan Liu
Fenfang Chen
Xin-Hua Feng
author_facet Yulan Zhao
Jinquan Liu
Fenfang Chen
Xin-Hua Feng
author_sort Yulan Zhao
collection DOAJ
description The epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process converting epithelial cells into mesenchymal cell morphology. Snail is a critical regulator of EMT by both suppressing epithelial gene expression and promoting mesenchymal gene expression. Expression and activity of Snail are tightly controlled at transcriptional and post-translational levels. It has previously been reported that Snail undergoes phosphorylation and ubiquitin-dependent proteasome degradation. Here, we report nuclear phosphatase SCP4/CTDSPL2 acts as a novel Snail phosphatase. SCP4 physically interacts with and directly dephosphorylates Snail. SCP4-mediated dephosphorylation of Snail suppresses the ubiquitin-dependent proteasome degradation of Snail and consequently enhances TGFβ-induced EMT. The knockdown of SCP4 in MCF10A mammary epithelial cells leads to attenuated cell migration. Collectively, our finding demonstrates that SCP4 plays a critical role in EMT through Snail dephosphorylation and stabilization.
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spelling doaj.art-efbcd26a8fab4f5e8f413463e117c3b32022-12-22T00:03:45ZengThe Royal SocietyOpen Biology2046-24412018-04-018410.1098/rsob.170274170274C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilizationYulan ZhaoJinquan LiuFenfang ChenXin-Hua FengThe epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process converting epithelial cells into mesenchymal cell morphology. Snail is a critical regulator of EMT by both suppressing epithelial gene expression and promoting mesenchymal gene expression. Expression and activity of Snail are tightly controlled at transcriptional and post-translational levels. It has previously been reported that Snail undergoes phosphorylation and ubiquitin-dependent proteasome degradation. Here, we report nuclear phosphatase SCP4/CTDSPL2 acts as a novel Snail phosphatase. SCP4 physically interacts with and directly dephosphorylates Snail. SCP4-mediated dephosphorylation of Snail suppresses the ubiquitin-dependent proteasome degradation of Snail and consequently enhances TGFβ-induced EMT. The knockdown of SCP4 in MCF10A mammary epithelial cells leads to attenuated cell migration. Collectively, our finding demonstrates that SCP4 plays a critical role in EMT through Snail dephosphorylation and stabilization.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170274snailctdspl2/scp4phosphatasetgf-β signallingphosphorylationemt
spellingShingle Yulan Zhao
Jinquan Liu
Fenfang Chen
Xin-Hua Feng
C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
Open Biology
snail
ctdspl2/scp4
phosphatase
tgf-β signalling
phosphorylation
emt
title C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
title_full C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
title_fullStr C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
title_full_unstemmed C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
title_short C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
title_sort c terminal domain small phosphatase like 2 promotes epithelial to mesenchymal transition via snail dephosphorylation and stabilization
topic snail
ctdspl2/scp4
phosphatase
tgf-β signalling
phosphorylation
emt
url https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170274
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AT fenfangchen cterminaldomainsmallphosphataselike2promotesepithelialtomesenchymaltransitionviasnaildephosphorylationandstabilization
AT xinhuafeng cterminaldomainsmallphosphataselike2promotesepithelialtomesenchymaltransitionviasnaildephosphorylationandstabilization