mTOR：自噬调节的药理学靶点。
mTOR: a pharmacologic target for autophagy regulation.
作者信息
Kim Young Chul, Guan Kun-Liang
出版信息
J Clin Invest. 2015 Jan;125(1):25-32. doi: 10.1172/JCI73939. Epub 2015 Jan 2.
Abstract
mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism. mTOR regulates cell growth and proliferation in response to a wide range of cues, and its signaling pathway is deregulated in many human diseases. mTOR also plays a crucial role in regulating autophagy. This Review provides an overview of the mTOR signaling pathway, the mechanisms of mTOR in autophagy regulation, and the clinical implications of mTOR inhibitors in disease treatment.
摘要
mTOR是一种丝氨酸/苏氨酸激酶，是细胞代谢的主要调节因子。mTOR响应多种信号调节细胞生长和增殖，其信号通路在许多人类疾病中失调。mTOR在调节自噬中也起着关键作用。本综述概述了mTOR信号通路、mTOR在自噬调节中的机制以及mTOR抑制剂在疾病治疗中的临床意义。
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本文引用的文献
1
The role for autophagy in cancer.
J Clin Invest. 2015 Jan;125(1):42-6. doi: 10.1172/JCI73941. Epub 2015 Jan 2.
2
Development of autophagy inducers in clinical medicine.
J Clin Invest. 2015 Jan;125(1):14-24. doi: 10.1172/JCI73938. Epub 2015 Jan 2.
3
Pharmacologic agents targeting autophagy.
J Clin Invest. 2015 Jan;125(1):5-13. doi: 10.1172/JCI73937. Epub 2015 Jan 2.
4
Rag GTPases are cardioprotective by regulating lysosomal function.
Nat Commun. 2014 Jul 1;5:4241. doi: 10.1038/ncomms5241.
5
RagA, but not RagB, is essential for embryonic development and adult mice.
Dev Cell. 2014 May 12;29(3):321-9. doi: 10.1016/j.devcel.2014.03.017. Epub 2014 Apr 24.
6
Regulation of mTORC1 by amino acids.
Trends Cell Biol. 2014 Jul;24(7):400-6. doi: 10.1016/j.tcb.2014.03.003. Epub 2014 Mar 31.
7
Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling.
Cell Death Dis. 2014 Feb 27;5(2):e1088. doi: 10.1038/cddis.2014.59.
8
Making new contacts: the mTOR network in metabolism and signalling crosstalk.
Nat Rev Mol Cell Biol. 2014 Mar;15(3):155-62. doi: 10.1038/nrm3757.
9
Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome.
Cell. 2014 Feb 13;156(4):771-85. doi: 10.1016/j.cell.2013.11.049.
10
Rapamycin: one drug, many effects.
Cell Metab. 2014 Mar 4;19(3):373-9. doi: 10.1016/j.cmet.2014.01.001. Epub 2014 Feb 6.
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