Yuan Xiaohan, Zhang Minghui, Ao Jinxia, Zhen Zhen, Gao Xuejun, Li Meng
The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China.
J Cell Physiol. 2019 Sep;234(9):15825-15835. doi: 10.1002/jcp.28240. Epub 2019 Feb 2.
Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) is a highly phosphorylated nuclear protein ubiquitously expressed in vertebrates. NUCKS1 has been reported to be a key chromatin modifier and transcriptional regulator of a number of signaling pathways, but the physiological role and detailed mechanism are still limited. In this study, we assessed the role of NUCKS1 on milk synthesis in and proliferation of mammary epithelial cells from a dairy cow. NUCKS1 was located in the nucleus of mammary epithelial cells, and the expression of NUCKS1 was stimulated by amino acids (Met and Leu) and hormones (estrogen and prolactin). Gene function study approaches detected that NUCKS1 positively regulated milk protein, milk fat, and lactose synthesis, and also increased the cell number, cell viability, and cell cycle progression. NUCKS1 mediated the stimulation of amino acids and hormones on the messenger RNA expression of the mechanistic target of rapamycin (mTOR), SREBP-1c, and Cyclin D1. The expression of NUCKS1 is dramatically higher in mouse mammary tissue of lactating period, compared with that in puberty and dry period. Taken together, these results reveal that NUCKS1 is a new mediator of milk synthesis in and proliferation of mammary epithelial cells via regulating the mTOR signaling pathway.
核内普遍存在的酪蛋白和细胞周期蛋白依赖性激酶底物1（NUCKS1）是一种在脊椎动物中普遍表达的高度磷酸化的核蛋白。据报道，NUCKS1是多种信号通路的关键染色质修饰因子和转录调节因子，但其生理作用和详细机制仍不明确。在本研究中，我们评估了NUCKS1对奶牛乳腺上皮细胞乳汁合成和增殖的作用。NUCKS1定位于乳腺上皮细胞的细胞核中，其表达受到氨基酸（蛋氨酸和亮氨酸）和激素（雌激素和催乳素）的刺激。基因功能研究方法检测到，NUCKS1对乳蛋白、乳脂和乳糖的合成具有正向调节作用，还能增加细胞数量、细胞活力和细胞周期进程。NUCKS1介导了氨基酸和激素对雷帕霉素作用靶点（mTOR）、固醇调节元件结合蛋白1c（SREBP-1c）和细胞周期蛋白D1（Cyclin D1）信使核糖核酸表达的刺激。与青春期和干奶期相比，NUCKS1在哺乳期小鼠乳腺组织中的表达显著更高。综上所述，这些结果表明，NUCKS1是通过调节mTOR信号通路来介导乳腺上皮细胞乳汁合成和增殖的新介质。
