Open AccessC-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization
Author(s) -
Yulan Zhao,
Jinquan Liu,
Fenfang Chen,
XinHua Feng
Publication year - 2018
Publication title -
open biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.078
H-Index - 53
ISSN - 2046-2441
DOI - 10.1098/rsob.170274
Subject(s) - snail , dephosphorylation , biology , microbiology and biotechnology , gene knockdown , phosphatase , phosphorylation , epithelial–mesenchymal transition , biochemistry , downregulation and upregulation , gene , ecology
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.