Journal Article

The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by α-T-catenin upregulation

Marie van Dijk, Jan van Bezu, Daan van Abel, Caroline Dunk, Marinus A. Blankenstein, Cees B.M. Oudejans and Stephen J. Lye

in Human Molecular Genetics

Volume 19, issue 13, pages 2658-2667
Published in print July 2010 | ISSN: 0964-6906
Published online April 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq152
The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by α-T-catenin upregulation

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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 α-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.

Journal Article.  5812 words.  Illustrated.

Subjects: Genetics and Genomics

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