六、mTOR是细胞自噬的核心 mTOR信号通路是调控细胞生长与增殖的一个 关键通路,该通路将营养、能量状态及生长因子信号整合在一起,并作为主要的调控因子参与细胞自 噬过程。mTOR有两种不同的复合体,即mTORC1和mTORC2。 mTORC1通过磷酸化使形成的自噬调节复合物(由ULK1和其互作蛋白Atg13、FIP200、Atg101等形成)失活,...
mTORC2通过磷酸化Akt(蛋白激酶B)和PKC(蛋白激酶C), 传递信号到小GTP酶Rac1和RhoA, 参与调节细胞骨架的形成。AMPK是细胞中感受能量状态调节代谢的一个蛋白激酶, 在自噬发生的调控中也发挥着重要的作用。低ATP水平状态下(如饥饿或缺氧) AMPK能感受AMP的水平变化而激活, 从而磷酸化加剧TSC1/2对Rheb的抑制, 最终使...
近日,华中农业大学动物科学技术学院、动物医学院晏向华教授课题组在专业期刊Autophagy(IF=16.02) 上发表了题为 KAT7-mediated CANX (calnexin) crotonylation regulates leucine-stimulated MTORC1 activity 的最新研究成果,揭示了KAT7介导的巴豆酰化修饰调控MTORC1通路的新机制,为营养物质尤其是亮氨酸调控机制提供了理论依据。
MTOR是一种高度保守的激酶,可以在饥饿、氧化应激、能量匮乏和病原体感染等恶劣条件下启动自噬。MTOR的抑制由ULK1/ULK2、RB1CC1、ATG13和ATG101组成的蛋白复合物激活,进而导致自噬体形成。此外,ATG7和ATG10参与ATG12-ATG5缀合物的生成,与ATG16L1、ATG7和ATG3共同参与Atg8家族蛋白的脂质化,调节自噬体与溶酶体的融合...
据报道，天然化合物姜黄素和熊果酸通过抑制多种癌症中的 PI3K-MTOR 通路来诱导自噬性细胞死亡。然而，这些分子溶解度低、稳定性差、吸收率低，导致它们的生物利用度低。因此，迫切需要安全有效的自噬诱导剂。机理模式图（图源自Autophagy ）CDK6(环蛋白依赖性激酶6)是一种丝氨酸/苏氨酸激酶，据报道与自噬密切相关。C...
mTORC2SGK-1The mechanistic target of rapamycin (mTOR) has gathered significant attention as a ubiquitously expressed multimeric kinase with key implications for cell growth, proliferation, and survival. This kinase forms the central core of two distinct complexes, mTORC1 and mTORC2, which share the...
mTOR switches cell metabolism to increased production of protein, lipids and nucleotides, while suppressing catabolic pathways. Most notably, mTOR inhibits the process of autophagy whereby intracellular components are engulfed in double-membraned vesicles, the autophagosomes, which ultimately fuse with lysos...
While less is known about mTORC2, the availability of acute small molecule inhibitors and multiple genetic models has led to increased understanding about the role of mTORC2 in autophagy. Emerging evidence suggests that the regulation of mTORC2 in autophagy is mainly through its downstream effector ...
(mTOR) signaling pathway and the complex of Beclin1 play a direct role in the regulation of autophagy.mTOR can be regulated by every upstream factor,as well as modulate the formation of downstream complex Atg1/ULK and eventually induce autophagy.Understanding of mTOR signaling pathway and its ...
Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J. Neurosci. 29, 1773–1783 (2009). Article CAS PubMed PubMed Central Google Scholar Zeng, L. H. et al. Tsc2 gene inactivation causes a more severe ...