Involvement of RNA binding proteins AUF1 in mammary gland differentiation
Involvement of RNA binding proteins AUF1 in mammary gland differentiation
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DOI：
10.1016/j.yexcr.2007.04.017
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发表时间：
2007-08-01
影响因子：
3.7
通讯作者：
Sakai, Senkiti
中科院分区：
文献类型：
--
作者：
Nagaoka, Kentaro;Tanaka, Tetsuya;Sakai, Senkiti
在乳腺上皮细胞分化过程中，乳源激素的刺激改变了许多基因的表达，如β-酪蛋白、c-myc和细胞周期蛋白D1。在这里，我们证明转录后调控在建立启动产奶所需的基因表达以及转录调控方面起着重要作用。AUF1蛋白是AU-Rich Element(ARE)结合蛋白家族中的一员，通过调节mRNA的稳定性和/或翻译控制，在ARE-mRNA的转换中发挥作用。AUF1蛋白的细胞质定位与功能密切相关。我们发现，随着乳腺的分化，AUF1蛋白从细胞质移动到细胞核。此外，在乳腺上皮细胞(HC11)中，促乳素刺激降低了胞浆AUF1的水平，增加了胞核AUF1的水平。AUF1蛋白可直接与c-myc基因结合，但不能与β-酪蛋白或细胞周期蛋白D1mRNA结合。AUF1下调HC11细胞的β-酪蛋白mRNA表达，并通过促乳激素降低c-myc mRNA的表达。相反，AUF1的过表达抑制了HC11细胞中促乳素刺激的这些效应。这些结果表明AUF1在促乳激素信号的调控下参与了乳腺分化过程。(C)2007年，爱思唯尔公司出版。
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. (c) 2007 Published by Elsevier Inc.