Department of Clinical Chemistry, VU University Medical Center, Amsterdam the Netherlands.
Hum Mol Genet. 2010 Jul 1;19(13):2658-67. doi: 10.1093/hmg/ddq152. Epub 2010 Apr 16.
By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein alpha-T-catenin (CTNNA3). This is effectuated at the crucial epithelial-mesenchymal transition of proliferative into invasive extravillous trophoblast. This STOX1-CTNNA3 interaction is direct and includes Akt-mediated phosphorylated control of nucleo-cytoplasmic shuttling and ubiquitin-mediated degradation as shared with the FOX multigene family. This, to our knowledge, is the first time a genotype associated with pre-eclampsia has been shown to directly limit first trimester extravillous trophoblast invasion, the earliest hallmark of pre-eclampsia.
通过使用互补的体外和离体方法，我们表明先兆子痫易感基因 STOX1 的风险等位基因（Y153H）通过上调细胞-细胞粘附蛋白α-连环蛋白（CTNNA3）来负调控滋养细胞浸润。这种作用发生在增殖性侵入性绒毛外滋养细胞的关键上皮-间充质转化过程中。这种 STOX1-CTNNA3 相互作用是直接的，包括 Akt 介导的核质穿梭的磷酸化控制和与 FOX 多基因家族共享的泛素介导的降解。据我们所知，这是首次表明与先兆子痫相关的基因型直接限制妊娠早期绒毛外滋养细胞浸润，这是先兆子痫的最早标志。
