蛋白质翻译是高度耗能的,并使用多种合成代谢途径,包括PPP和谷氨酰胺水解。AMPK通过抑制mTORC1和翻译机制,允许癌细胞适应恶劣的营养条件,如葡萄糖剥夺。 主要参考文献 Jordan H. Driskill et al,The Hippo Pathway in Liver Homeostasis and Pathophysiology. Annu Rev Pathol. 2021 January 24; 16: 299–322 Rober...
mTOR抑制剂是第一批进入临床应用的PAM靶向药物。mTOR抑制剂可分为三类:第一代异构性(非竞争性)mTOR抑制剂(异构性mTORi),仅抑制mTORC1;第二代ATP竞争性mTOR抑制剂(ATP竞争性 mTORi),可抑制mTORC1和mTORC2;第三代双手性mTOR抑制剂(双手性mTORi), 仅抑...
mTORC1和mTORC2在肾脏中广泛表达,其活性依赖于PI3K/Akt信号通路的调控。激活的Akt在Ser2448位点磷酸化mTOR,可直接激活mTORC1;通过抑制结节性硬化症复合体(TSC)1和TSC2,间接激活mTORC1。当mTORC1被激活时,下游的RAS超家族GTP酶(Rheb-GT...
活化Akt可使其发挥包括调节细胞代谢(如通过激活AS160)、控制细胞生长(如通过TSC1/TSC2和mTORC1信号通路)、促进细胞存活(如通过抑制促凋亡蛋白Bad)和刺激增殖(如通过磷酸化p21)等功能4。磷酸酶和张力素同源物(PTEN)是Akt重要的负调控因子,使PIP3去磷酸化,发挥抑癌作用。 Akt失调和疾病 在不同的疾病状态中都有Akt...
我们的研究结果表明,Fatostatin处理通过抑制GBM中的AKT/mTORC1/GPX4信号通诱导GPX4介导的铁死亡。此外,Fatostatin诱导的细胞增殖和EMT的抑制也归因于AKT/mTORC1信号传导途径。为了克服BBB的阻碍,我们设计了装载Fatostatin的p28功能化PLGA纳米颗粒,并证明它们可以显著增加到达颅内肿瘤的药物剂量,并明显抑制肿瘤生长。
The alterations of metabolism in the m.3243 A > G mutant cells strongly imply a perturbation in cell signalling, especially implicating the PI3K-Akt-mTORC1 pathway, which has been widely studied in cancer signalling and metabolism25. For example, oxidative stress and redox imbalance may ac...
TSC1/2:抑制TSC1/2磷酸化,激活mTORC1,增加蛋白质合成protein synthesis,减少细胞自噬(autophagy)。 mTOR FOXO:通过磷酸化抑制FOXO,增加细胞存活(cell survival)以及增殖 GSK3:激活糖原合成(glycogen synthesis) Other:增加脂肪酸合成 如何关闭AKT信号通路:
Moreover, co-treatment of PTEN inhibitor re-activated the PI3K/AKT/mTORC1 pathway, therefore counteracting the pro-autophagic and anti-hypertrophic effects of miR302–367 depletion on cardiomyocytes. These findings unveiled the pivotal role of the miR302–367 cluster in regulating cardiac autophagy ...
mTORC1 activation must be tightly balanced following denervation. Acutely activating or inhibiting mTORC1 impairs autophagy regulation and alters homeostasis in denervated muscle. Importantly, PKB/Akt inhibition, conferred by sustained mTORC1 activation, abrogates denervation-induced synaptic remodeling and ca...
Recent findings indicate that pathway integrates signals from growth factors and nutrients with , , cell size, remodeling and mitochondrial metabolism. is a part of two distinct complexes; mTORC1 and mTORC2. The mammalian is sensitive to and contains , deptor, and the G protein β-subunit-like...