Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
Department of Agricultural Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
Biochem Biophys Res Commun. 2021 Feb 19;541:84-89. doi: 10.1016/j.bbrc.2021.01.033. Epub 2021 Jan 20.
Tuberous sclerosis complex 2 (TSC2) is a tumor-suppressor protein that is partially regulated by insulin, energy, oxygen, and growth factors. Mutations in the TSC2 gene and loss of TSC2 promote cell growth by the mammalian target of rapamycin complex 1 (mTORC1) activation. Furthermore, S-adenosylmethionine (SAM) sensor upstream of mTORC1 indirectly inhibits mTORC1 activity via the methionine metabolite SAM. Here, we investigated the effects of methionine on insulin/TSC2/mTORC1 activity. Our results showed that methionine affected TSC2 stability and abolished TSC2 localization to the lysosome. Moreover, activation of insulin signaling contributed to TSC2 degradation in a methionine deprivation-dependent manner. Thus, methionine and insulin crosstalk occurred via TSC2.
结节性硬化症复合征 2（TSC2）是一种肿瘤抑制蛋白，部分受胰岛素、能量、氧气和生长因子调节。TSC2 基因突变和 TSC2 缺失通过哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）的激活促进细胞生长。此外，mTORC1 上游的 S-腺苷甲硫氨酸（SAM）传感器通过甲硫氨酸代谢物 SAM 间接抑制 mTORC1 活性。在这里，我们研究了蛋氨酸对胰岛素/TSC2/mTORC1 活性的影响。我们的结果表明，蛋氨酸影响 TSC2 的稳定性并使 TSC2 定位到溶酶体中。此外，胰岛素信号的激活有助于 TSC2 在依赖蛋氨酸剥夺的情况下降解。因此，蛋氨酸和胰岛素通过 TSC2 发生相互作用。
