SESN2 negatively regulates cell proliferation and casein synthesis by inhibition the amino acid-mediated mTORC1 pathway in cow mammary epithelial cells

Amino acids (AA) are one of the key nutrients that regulate cell proliferation and casein synthesis in cow mammary epithelial cells (CMEC), but the mechanism of this regulation is not yet clear. In this study, the effect of SESN2 on AA-mediated cell proliferation and casein synthesis in CMEC was assessed. After 12 h of AA starvation, CMECs were cultured in the absence of all AA (AA-), in the presences of only essential AA (EAA+), or of all AA (AA+). Cell proliferation, casein expression, and activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway were increased; but SESN2 expression was decreased in response to increased EAA or AA supply. Overexpressing or inhibiting SESN2 demonstrated that cell proliferation, casein expression, and activation of the mTORC1 pathway were all controlled by SESN2 expression. Furthermore, the increase in cell proliferation, casein expression, and activation of the mTORC1 pathway in response to AA supply was inhibited by overexpressing SESN2, and those effects were reversed by inhibiting SESN2. These results indicate that SESN2 is an important inhibitor of mTORC1 in CMEC blocking AA-mediated cell proliferation and casein synthesis.