NUCKS1 is a novel regulator of milk synthesis in and proliferation of mammary epithelial cells via the mTOR signaling pathway.

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.