Cyclase-associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells
Cyclase-associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells
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环化酶相关蛋白1是牛乳腺上皮细胞乳汁合成和增殖的关键负调节因子
DOI：
10.1002/cbf.3387
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发表时间：
2019
影响因子：
3.6
通讯作者：
Ao Jin xia
中科院分区：
文献类型：
--
作者：
Yuan Xiaohan;Zhen Zhen;Zhang Minghui;Yu Yanbo;Gao Xuejun;Ao Jin xia
腺苷酸环化酶相关蛋白（CAP）是一种高度保守的蛋白质。先前的报道表明，CAP 1可能是细胞增殖、迁移和粘附以及细胞癌发展的负调节因子。CAP 1调控下游通路的分子机制，以及CAP 1如何受环境刺激和上游信号转导的调控，目前还不清楚。在本研究中，我们评估了CAP 1在牛奶合成和牛乳腺上皮细胞增殖中的作用。使用基因过表达和沉默方法，发现CAP 1通过PI 3 K-mTOR/SREBP-1c/Cyclin D1信号通路负调节乳汁合成和细胞增殖。激素，如催乳素和雌激素，和氨基酸，如甲硫氨酸和亮氨酸，刺激MMP 9的表达和触发CAP 1降解，并因此，消除其抑制牛奶蛋白质，脂肪和乳糖的合成和增殖的牛乳腺上皮细胞。我们的研究结果有助于加深我们对牛奶合成调控机制的理解，并有助于描述CAP 1的分子机制。以往的研究表明，CAP 1是细胞增殖和凋亡的负调控因子，但其分子机制尚不清楚。在本研究中，我们确定CAP 1作为牛奶合成和增殖的牛乳腺上皮细胞的负调节。我们的研究结果将加深我们对牛奶合成的调控机制的理解，并有助于探索CAP 1的分子机制。
Adenylyl cyclase‐associated protein (CAP) is a highly conserved protein. Previous reports have suggested that CAP1 may be a negative regulator of cellular proliferation, migration, and adhesion and the development of cell carcinomas. The molecular mechanism of CAP1 regulation of downstream pathways, as well as how CAP1 is regulated by environmental stimuli and upstream signalling, is not well understood. In this present study, we assessed the role of CAP1 in milk synthesis and proliferation of bovine mammary epithelial cells. Using gene overexpression and silencing methods, CAP1 was found to negatively regulate milk synthesis and proliferation of cells via the PI3K‐mTOR/SREBP‐1c/Cyclin D1 signalling pathway. Hormones, such as prolactin and oestrogen, and amino acids, such as methionine and leucine, stimulate MMP9 expression and trigger CAP1 degradation, and thus, abrogate its inhibition of synthesis of milk protein, fat, and lactose by and proliferation of bovine mammary epithelial cells. The results of our study help deepen our understanding of the regulatory mechanisms underlying milk synthesis and aid in characterizing the molecular mechanisms of CAP1.Previous reports have suggested that CAP1 is a negative regulator of cellular proliferation and anabolism, but the molecular mechanisms are largely unknown. In this present study, we identified CAP1 as a negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells. Our results will deepen our understanding of the regulatory mechanisms underlying milk synthesis and aid in exploring the molecular mechanisms of CAP1.