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细胞中p53和mTOR信号通路的协同调控

The coordinate regulation of the p53 and mTOR pathways in cells.

作者信息

Feng Zhaohui, Zhang Haiyan, Levine Arnold J, Jin Shengkan

机构信息

Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.

出版信息

Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8204-9. doi: 10.1073/pnas.0502857102. Epub 2005 May 31.

Abstract

Cell growth and proliferation requires an intricate coordination between the stimulatory signals arising from nutrients and growth factors and the inhibitory signals arising from intracellular and extracellular stresses. Alteration of the coordination often causes cancer. In mammals, the mTOR (mammalian target of rapamycin) protein kinase is the central node in nutrient and growth factor signaling, and p53 plays a critical role in sensing genotoxic and other stresses. The results presented here demonstrate that activation of p53 inhibits mTOR activity and regulates its downstream targets, including autophagy, a tumor suppression process. Moreover, the mechanisms by which p53 regulates mTOR involves AMP kinase activation and requires the tuberous sclerosis (TSC) 1/TSC2 complex, both of which respond to energy deprivation in cells. In addition, glucose starvation not only signals to shut down mTOR, but also results in the transient phosphorylation of the p53 protein. Thus, p53 and mTOR signaling machineries can cross-talk and coordinately regulate cell growth, proliferation, and death.

摘要

细胞生长和增殖需要营养物质和生长因子产生的刺激信号与细胞内和细胞外应激产生的抑制信号之间进行复杂的协调。这种协调的改变常常会引发癌症。在哺乳动物中,mTOR(雷帕霉素的哺乳动物靶点)蛋白激酶是营养物质和生长因子信号传导的中心节点,而p53在感知基因毒性和其他应激方面发挥着关键作用。此处呈现的结果表明,p53的激活会抑制mTOR活性并调节其下游靶点,包括自噬,这是一种肿瘤抑制过程。此外,p53调节mTOR的机制涉及AMP激酶的激活,并且需要结节性硬化症(TSC)1/TSC2复合物,这两者都对细胞内的能量剥夺作出反应。此外,葡萄糖饥饿不仅会发出关闭mTOR的信号,还会导致p53蛋白的瞬时磷酸化。因此,p53和mTOR信号传导机制可以相互作用并协调调节细胞的生长、增殖和死亡。

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本文引用的文献

1
Dysregulation of the TSC-mTOR pathway in human disease.
Nat Genet. 2005 Jan;37(1):19-24. doi: 10.1038/ng1494.
2
The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis.
Science. 2004 Oct 22;306(5696):695-8. doi: 10.1126/science.1100537.
3
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.
Nat Cell Biol. 2004 Nov;6(11):1122-8. doi: 10.1038/ncb1183. Epub 2004 Oct 3.
4
Methods for monitoring autophagy.
Int J Biochem Cell Biol. 2004 Dec;36(12):2491-502. doi: 10.1016/j.biocel.2004.02.005.
5
Regulation and role of autophagy in mammalian cells.
Int J Biochem Cell Biol. 2004 Dec;36(12):2445-62. doi: 10.1016/j.biocel.2004.02.002.
6
Upstream and downstream of mTOR.
Genes Dev. 2004 Aug 15;18(16):1926-45. doi: 10.1101/gad.1212704.
7
TOR signaling.
Sci STKE. 2003 Dec 9;2003(212):re15. doi: 10.1126/stke.2122003re15.
8
Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15077-82. doi: 10.1073/pnas.2436255100. Epub 2003 Dec 1.
9
TSC2 mediates cellular energy response to control cell growth and survival.
Cell. 2003 Nov 26;115(5):577-90. doi: 10.1016/s0092-8674(03)00929-2.
10
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.
J Clin Invest. 2003 Dec;112(12):1809-20. doi: 10.1172/JCI20039. Epub 2003 Nov 24.

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