2024年10月9日 · Bafilomycin A1 (BafA1) is a macrolide antibiotic that blocks lysosomal function by targeting the v-ATPase (vacuolar H + ATPase), causing alkalinization of the lysosomal lumen and...

2024年11月21日 · S6K is a downstream target and key effector of mTORC1-dependent processes like protein synthesis. 34 Unlike rapamycin, treatment with two independent S6K inhibitors that abolished phosphorylation of its direct target S6 (Figure S2 D) did not influence mTOR localization in cells (Figures S2 E and S2F), further suggesting that changes in the ...

2019年11月11日 · Here we show that autophagy supports mTORC1 hyperactivation in neural stem cells (NSCs) lacking tuberous sclerosis complex subunit 1 (Tsc1), thereby promoting defects in NSC maintenance,...

2023年12月15日 · BafA1 is an inhibitor of vacuolar H + ATPase (V-ATPase), and by preventing acidification and subsequent lysosomal degradation of cargoes, it is used to measure autophagy flux. However, MORG1 was not degraded through the lysosome, and p62 KO did not affect MORG1 levels under basal conditions in HeLa ( Figures S1 C and S1D) or HEK293 cells ...

2021年4月17日 · We have previously shown that S6K1 kinase is essential for autophagic flux under stress conditions. Here, we aimed to elucidate the underlying mechanism of S6K1 involvement in autophagy. We stimulated autophagy in S6K1/2 double-knockout mouse embryonic fibroblasts by exposing them to different stress conditions.

2023年9月7日 · Strikingly, the half maximal inhibitory concentration (IC 50) of ConA on inhibiting Dox-induced UPR mt is below 1.5 nM in MEFs, while that of BafA1 is around 50 nM (Fig. 1c), in line with a more...

mTORC1在细胞溶酶体表面激活，磷酸化下游底物： S6K激酶 、 4E-BP1 和转录因子 TFEB 等来促进细胞的合成代谢。 生长因子、氨基酸和葡萄糖能量水平改变都可调控mTORC的活性。生长因子的加入可解除TSC对GTPase Rheb 的抑制。

2021年3月23日 · The autophagy inhibitor BafA1, when combined with the AKT inhibitor MK2206, caused a robust sensitization of the cells to endoxifen. This indicates that autophagy activated upon AKT inhibition contributes to endoxifen resistance.

2020年2月6日 · Bafilomycin A1 (BafA1), a macrolide, potently inhibits the v-ATPase pump and prevents acidification of lysosomes (Figure 1 A) (Bowman et al., 1988). Both compounds cause cell death at high concentrations and only mildly inhibit …

2012年1月1日 · 核糖体蛋白 S6K（S6 激酶）代表了 TORC1 [TOR（雷帕霉素靶点）复合物 1] 的一种广泛研究的效应物，其在细胞和生物体生理学中具有重要但尚未完全确定的作用。 TORC1 通过整合来自不同环境线索的信号来促进合成代谢和抑制分解代谢细胞功能，从而起到环境传感器的作用。 mTORC1（哺乳动物 TORC1）磷酸化并激活 S6K1 和 S6K2，其第一个鉴定的底物是 rpS6（核糖体蛋白 S6），它是 40S 核糖体的一个组成部分。 过去十年的研究发现了许多额 …