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...
Main Authors: | , , , |
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Format: | Article |
Language: | English |
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The Royal Society
2018-04-01
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Series: | Open Biology |
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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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id | doaj.art-efbcd26a8fab4f5e8f413463e117c3b3 |
institution | Directory Open Access Journal |
issn | 2046-2441 |
language | English |
last_indexed | 2024-12-13T01:41:22Z |
publishDate | 2018-04-01 |
publisher | The Royal Society |
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series | Open Biology |
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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