C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization.
C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization.
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C 端结构域小磷酸酶样 2 通过 Snail 去磷酸化和稳定化促进上皮细胞向间质细胞的转变。
DOI：
10.1098/rsob.170274
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发表时间：
2018-04
期刊：
影响因子：
5.8
通讯作者：
Feng XH
中科院分区：
文献类型：
--
作者：
Zhao Y;Liu J;Chen F;Feng XH
上皮向间充质转化(EMT)是一种将上皮细胞转化为间充质细胞形态的细胞重编程过程。Snail通过抑制上皮细胞基因表达和促进间充质细胞基因表达，是EMT的重要调节因子。Snail的表达和活性在转录和翻译后水平受到严格控制。此前有报道称，Snail经历了磷酸化和泛素依赖的蛋白酶体降解。在此，我们报道了核磷酸酶SCP4/CTDSPL2作为一种新的蜗牛磷酸酶。SCP4在物理上与Snail相互作用并直接使Snail去磷酸化。SCP4介导的Snail去磷酸化抑制了Snail依赖泛素的蛋白酶体的降解，从而增强了转化生长因子β诱导的内皮细胞转化。在MCF10A乳腺上皮细胞中，SCP4基因被敲除，导致细胞迁移减弱。总而言之，我们的发现表明，SCP4通过Snail去磷酸化和稳定化在EMT中发挥关键作用。
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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影响因子：
--
作者：
Azmi AS;Bollig-Fischer A;Bao B;Park BJ;Lee SH;Yong-Song G;Dyson G;Reddy CK;Sarkar FH;Mohammad RM
通讯作者：
Mohammad RM
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
10.5
作者：
Winston, JT;Strack, P;Harper, JW
通讯作者：
Harper, JW
影响因子：
4.8
作者：
Villarejo, Ana;Cortes-Cabrera, Alvaro;Cano, Amparo
通讯作者：
Cano, Amparo
影响因子：
11.8
作者：
Dai, Fangyan;Lin, Xia;Chang, Chenbei;Feng, Xin-Hua
通讯作者：
Feng, Xin-Hua