β-Catenin (CTNNB1) in the Mouse Uterus During Decidualization and the Potential Role of Two Pathways in Regulating Its Degradation

Abstract

β-catenin plays a role in cell adhesion and as a transcriptional coactivator. Its levels are regulated in cells by controlling its degradation through ubiquitination by two different E3 ligase complexes. One complex contains β-transducing repeat containing (BTRC) protein, which binds to β-catenin when phosphorylated on specific (S33 and S37) residues, whereas the other involves calcyclin-binding protein (CACYBP). The aim of this study was to determine the localization and levels of total and active (S33/S37-dephosphorylated) β-catenin in the pregnant mouse uteri and those undergoing artificially stimulated decidualization. These two forms of β-catenin were localized almost exclusively to the endometrial epithelia just prior to the onset of implantation. Although this localization continued after the onset of implantation, there were less epithelial cells present in areas of the uterus undergoing decidualization. Rather, there was a progressive increase in β-catenin localization in endometrial stromal cells undergoing decidualization in the anti-mesometrial and, to a lesser extent, in the mesometrial regions. The presence of a conceptus was not required for the changes in localization seen in the pregnant uterus because similar findings were also seen in uteri undergoing artificially stimulated decidualization. Finally, overall levels of total, active (S33 and S37 dephosphorylated), and phosphorylated (S33/S37/T42) β-catenin protein and the steady-state levels of calcyclin-binding protein mRNA changed in the uterus during decidualization. The result of this study shows the changing localization and levels of β-catenin in the mouse uterus during decidualization. Further, the results suggest potential roles for both the BTRC and CACYBP E3 ligase mechanisms of β-catenin ubiquitination in the uterus during decidualization.