The Key Laboratory of Dairy Science of Education Ministry, College of Life Science, Northeast Agricultural University, Harbin, China.
School of Animal Science, Yangtze University, Jingzhou, China.
Biochem Biophys Res Commun. 2020 Aug 27;529(3):569-574. doi: 10.1016/j.bbrc.2020.05.193. Epub 2020 Jul 15.
The nuclear receptor co-activator 5 (NCOA5) is known as a co-activator or co-repressor that influences gene expression and cellular physiology, but its roles and detailed molecular mechanism is still largely unknown. In this study, we explored the role and molecular mechanism of NCOA5 in amino acid-induced activation of the mechanistic target of rapamycin (mTOR) and milk protein synthesis in bovine mammary epithelial cells (BMECs). Methionine (Met) and leucine (Leu) significantly up-regulated the expression of NCOA5. NCOA5 overexpression increased mTOR phosphorylation and β-casein synthesis, whereas its knockdown exhibited the opposite effects. Furthermore, inhibition of phosphatidylinositol 3-kinase (PI3K) completely abolished the stimulatory effects of Met and Leu on NCOA5 expression. ChIP-qPCR analysis detected that NCOA5 bound to the mTOR promoter, and this interaction was enhanced by the stimulation of Met and Leu. These above data reveal that NCOA5 is a key regulator of amino acid-induced PI3K-mediated mTOR activation and β-casein synthesis in BMECs.
核受体共激活因子 5（NCOA5）是一种共激活因子或共抑制因子，它可以影响基因表达和细胞生理，但它的作用和详细的分子机制在很大程度上仍然未知。在这项研究中，我们探讨了 NCOA5 在氨基酸诱导的雷帕霉素（mTOR）机制靶点激活和牛乳腺上皮细胞（BMEC）乳蛋白合成中的作用和分子机制。蛋氨酸（Met）和亮氨酸（Leu）显著上调了 NCOA5 的表达。NCOA5 的过表达增加了 mTOR 的磷酸化和 β-酪蛋白的合成，而其敲低则表现出相反的效果。此外，PI3K 的抑制剂完全消除了 Met 和 Leu 对 NCOA5 表达的刺激作用。ChIP-qPCR 分析检测到 NCOA5 与 mTOR 启动子结合，这种相互作用在 Met 和 Leu 的刺激下增强。这些数据表明，NCOA5 是氨基酸诱导的 PI3K 介导的 mTOR 激活和 BMEC 中β-酪蛋白合成的关键调节因子。
