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mTOR 对 TFEB 的调控作用。

TFEBulous control of traffic by mTOR.

机构信息

Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.

出版信息

EMBO J. 2011 Aug 17;30(16):3215-6. doi: 10.1038/emboj.2011.258.

DOI:10.1038/emboj.2011.258
PMID:21847138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3160668/
Abstract

EMBO J 30 16, 3242–3258 (2011); published online July 29 2011 Cell growth is accompanied by the synthesis of macromolecules and biogenesis of organelles. The protein kinase mTOR (mechanistic or mammalian target of rapamycin) controls these processes by sensing availability of growth signals. The targeting of macromolecules and trafficking of cargo-containing vesicles into appropriate cellular compartments are also important processes that are highly controlled during growth versus stress conditions. In this issue of , Peña-Llopis demonstrate that mTOR complex 1 (mTORC1) could regulate endocytosis by controlling the expression of endosomal proteins such as the vacuolar (V)-ATPases. mTORC1 performs this novel function by modulating the phosphorylation and activity of the transcription factor EB (TFEB), which is required for expression of genes involved in autophagosome and lysosome biogenesis. This study, along with a related study in by Settembre , reveals how growth signals mediated by mTOR and other protein kinases such as mitogen-activated protein kinase (MAPK) can converge on TFEB to direct endosome biogenesis and trafficking.

摘要

EMBO J 30 16, 3242–3258 (2011); published online July 29 2011 细胞生长伴随着大分子的合成和细胞器的生物发生。蛋白激酶 mTOR(机械或哺乳动物雷帕霉素靶)通过感知生长信号的可用性来控制这些过程。大分子的靶向和含有货物的囊泡运输到适当的细胞区室也是在生长与应激条件下高度控制的重要过程。在本期的 中,Peña-Llopis 证明 mTOR 复合物 1(mTORC1)可以通过控制内体蛋白(如液泡(V)-ATP 酶)的表达来调节内吞作用。mTORC1 通过调节转录因子 EB(TFEB)的磷酸化和活性来发挥这一新颖功能,TFEB 是参与自噬体和溶酶体生物发生的基因表达所必需的。这项研究与 Settembre 在 中的一项相关研究一起,揭示了由 mTOR 和其他蛋白激酶(如丝裂原活化蛋白激酶(MAPK))介导的生长信号如何可以汇聚到 TFEB 上,从而指导内体生物发生和运输。

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本文引用的文献

1
Regulation of TFEB and V-ATPases by mTORC1.mTORC1 对 TFEB 和 V-ATPases 的调节。
EMBO J. 2011 Jul 29;30(16):3242-58. doi: 10.1038/emboj.2011.257.
2
TFEB links autophagy to lysosomal biogenesis.TFEB 将自噬与溶酶体生物发生联系起来。
Science. 2011 Jun 17;332(6036):1429-33. doi: 10.1126/science.1204592. Epub 2011 May 26.
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mTOR: from growth signal integration to cancer, diabetes and ageing.mTOR:从生长信号整合到癌症、糖尿病和衰老。
Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35. doi: 10.1038/nrm3025. Epub 2010 Dec 15.
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Regulation of mammalian autophagy in physiology and pathophysiology.哺乳动物自噬在生理和病理生理学中的调控。
Physiol Rev. 2010 Oct;90(4):1383-435. doi: 10.1152/physrev.00030.2009.
5
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.Ragulator-Rag 复合物将 mTORC1 靶向到溶酶体表面,并且对于其被氨基酸激活是必需的。
Cell. 2010 Apr 16;141(2):290-303. doi: 10.1016/j.cell.2010.02.024. Epub 2010 Apr 8.
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Mol Cell. 2008 Mar 14;29(5):541-51. doi: 10.1016/j.molcel.2007.12.023.
9
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology.液泡型ATP酶:生理与病理生理学中的旋转质子泵
Nat Rev Mol Cell Biol. 2007 Nov;8(11):917-29. doi: 10.1038/nrm2272.