mTOR-Dependent Cell Survival Mechanisms
mTOR-Dependent Cell Survival Mechanisms
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DOI：
10.1101/cshperspect.a008771
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发表时间：
2012-12-01
影响因子：
7.2
通讯作者：
Guertin, David A.
中科院分区：
文献类型：
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作者：
Hung, Chien-Min;Garcia-Haro, Luisa;Guertin, David A.
雷帕霉素（mTOR）激酶的机制靶点是细胞生长、增殖和存活的保守调节剂。在细胞中，mTOR是mTORC 1和mTORC 2两种复合物的催化亚基，它们具有不同的上游调控信号和下游底物。mTORC1直接感知细胞营养物质的可用性，同时通过生长因子信号通路间接感知循环营养物质。限制生长的细胞应激也会影响mTORC 1活性。mTORC2不太清楚，似乎只感测生长因子。作为多种生长调节信号的整合者，mTOR进化为控制细胞代谢和能量稳态的中心信号传导枢纽，并且mTOR信号传导的缺陷在癌症、糖尿病和衰老的病理学中是重要的。在这里，我们讨论的机制，每个mTOR复合物可能会调节细胞的生存代谢和其他压力。
The mechanistic target of rapamycin (mTOR) kinase is a conserved regulator of cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit of two complexes called mTORC1 and mTORC2, which have distinct upstream regulatory signals and downstream substrates. mTORC1 directly senses cellular nutrient availability while indirectly sensing circulating nutrients through growth factor signaling pathways. Cellular stresses that restrict growth also impinge on mTORC1 activity. mTORC2 is less well understood and appears only to sense growth factors. As an integrator of diverse growth regulatory signals, mTOR evolved to be a central signaling hub for controlling cellular metabolism and energy homoeostasis, and defects in mTOR signaling are important in the pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which each mTOR complex might regulate cell survival in response to metabolic and other stresses.