Herington Jennifer L, Bi JiaJia, Martin John D, Bany Brent M
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
J Histochem Cytochem. 2007 Sep;55(9):963-74. doi: 10.1369/jhc.7A7199.2007. Epub 2007 May 28.
Beta-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 beta-transducing repeat containing (BTRC) protein, which binds to beta-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) beta-catenin in the pregnant mouse uteri and those undergoing artificially stimulated decidualization. These two forms of beta-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 beta-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) beta-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 beta-catenin in the mouse uterus during decidualization. Further, the results suggest potential roles for both the BTRC and CACYBP E3 ligase mechanisms of beta-catenin ubiquitination in the uterus during decidualization.
β-连环蛋白在细胞黏附中发挥作用,并作为转录共激活因子。其水平在细胞中通过两种不同的E3连接酶复合物介导的泛素化作用来控制其降解进行调节。一种复合物包含含β-转导重复序列(BTRC)的蛋白,该蛋白在特定(S33和S37)残基磷酸化时与β-连环蛋白结合,而另一种复合物涉及钙周期蛋白结合蛋白(CACYBP)。本研究的目的是确定妊娠小鼠子宫以及人工诱导蜕膜化的小鼠子宫中总β-连环蛋白和活性(S33/S37去磷酸化)β-连环蛋白的定位和水平。在着床开始前,这两种形式的β-连环蛋白几乎仅定位于子宫内膜上皮细胞。尽管着床开始后这种定位仍持续存在,但在发生蜕膜化的子宫区域中上皮细胞较少。相反,在子宫抗系膜侧以及程度较轻的系膜侧发生蜕膜化的子宫内膜基质细胞中,β-连环蛋白的定位逐渐增加。妊娠子宫中观察到的定位变化并不需要有孕体存在,因为在人工诱导蜕膜化的子宫中也观察到了类似的结果。最后,在蜕膜化过程中,子宫中总β-连环蛋白、活性(S33和S37去磷酸化)β-连环蛋白以及磷酸化(S33/S37/T42)β-连环蛋白的总体水平以及钙周期蛋白结合蛋白mRNA的稳态水平发生了变化。本研究结果显示了蜕膜化过程中小鼠子宫中β-连环蛋白定位和水平的变化。此外,结果提示在蜕膜化过程中,BTRC和CACYBP E3连接酶介导的β-连环蛋白泛素化机制在子宫中可能发挥潜在作用。