Nuclear Factor of κB1 Is a Key Regulator for the Transcriptional Activation of Milk Synthesis in Bovine Mammary Epithelial Cells.
The nuclear factor of κB (NFκB) family has been well known for its significant role in regulating the expression of numerous genes that control many biological processes. However, it is unclear whether NFκB could regulate milk synthesis. In this study, we identified NFκB1 as a critical regulator for milk synthesis in bovine mammary epithelial cells (BMECs). Gene function study revealed that NFκB1 modulates the expression of mammalian target of rapamycin (mTOR), sterol response element-binding protein (SREBP)-1c, and β4Gal-T2 for milk synthesis. Furthermore, chromatin immunoprecipitation assays showed that both methionine (Met) and estrogen (E) triggered NFκB1 to bind to gene promoters of mTOR, SREBP-1c, and β4Gal-T2 in BMECs. In addition, we confirmed that Met and E triggered NFκB1 expression and phosphorylation via phosphatidylinositol-3-kinase (PI3K) but not mTOR signaling pathway. Taken together, our study reveals that NFκB1 acts as a PI3K but not mTOR-dependent critical mediator for the transcriptional activation of signaling molecules regulating milk synthesis in BMECs.
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Xin
X
Huang
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Yanli
Y
Zang
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Minghui
M
Zhang
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Xiaohan
X
Yuan
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Meng
M
Li
The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University , Harbin, China .
Xuejun
X
Gao
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis* / Q000235:genetics; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D008894:Milk Proteins; D052002:NF-kappa B p50 Subunit; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases
NFκB1; PI3K; mammary epithelial cells; milk synthesis