Nagaoka Kentaro, Tanaka Tetsuya, Imakawa Kazuhiko, Sakai Senkiti
Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo, Japan.
Exp Cell Res. 2007 Aug 1;313(13):2937-45. doi: 10.1016/j.yexcr.2007.04.017. Epub 2007 Apr 20.
The expression of many genes, such as beta-casein, c-myc, and cyclin D1, is altered by lactogenic hormone stimulation during mammary epithelial cell differentiation. Here, we demonstrate that post-transcriptional regulation plays an important role to establish gene expression required to initiate milk production as well as transcriptional control. AUF1 protein, a member of the AU-rich element (ARE)-binding protein family, plays a role in ARE-mRNA turnover by regulating mRNA stability and/or translational control. Cytoplasmic localization of AUF1 protein is critically linked to function. We show that as the mammary gland differentiates, AUF1 protein moves from the cytoplasm to the nucleus. Moreover, in mammary gland epithelial cells (HC11), stimulation by lactogenic hormone decreased cytoplasmic and increased nuclear AUF1 levels. Direct binding of AUF1 protein was observed on c-myc mRNA, but not beta-casein or cyclin D1 mRNA. AUF1 downregulation in HC11 cells increased the expression of beta-casein mRNA and decreased the expression of c-myc mRNA by lactogenic hormone. Conversely, overexpression of AUF1 inhibited these effects of lactogenic hormone stimulation in HC11 cells. These results suggest that AUF1 participates in mammary gland differentiation processes under the control of lactogenic hormone signals.
在乳腺上皮细胞分化过程中，许多基因的表达，如β-酪蛋白、c-myc和细胞周期蛋白D1，会受到催乳激素刺激的影响而发生改变。在此，我们证明转录后调控在建立启动乳汁分泌所需的基因表达以及转录控制方面发挥着重要作用。富含AU元件（ARE）结合蛋白家族成员AUF1蛋白，通过调节mRNA稳定性和/或翻译控制，在ARE-mRNA周转中发挥作用。AUF1蛋白的细胞质定位与其功能密切相关。我们发现，随着乳腺的分化，AUF1蛋白从细胞质转移到细胞核。此外，在乳腺上皮细胞（HC11）中，催乳激素刺激会降低细胞质中AUF1水平并增加细胞核中AUF1水平。观察到AUF1蛋白直接结合在c-myc mRNA上，但不结合β-酪蛋白或细胞周期蛋白D1 mRNA。HC11细胞中AUF1的下调会增加催乳激素刺激下β-酪蛋白mRNA的表达并降低c-myc mRNA的表达。相反，AUF1的过表达会抑制HC11细胞中催乳激素刺激的这些效应。这些结果表明，AUF1在催乳激素信号的控制下参与乳腺分化过程。
