mTOR: from growth signal integration to cancer, diabetes and ageing

被引：3224

作者：

Zoncu, Roberto ^{[1
]}

Efeyan, Alejo ^{[1
]}

Sabatini, David M. ^{[1
,2
,3
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[3] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

NATURE REVIEWS MOLECULAR CELL BIOLOGY | 2011年 / 12卷 / 01期

基金：

美国国家卫生研究院;

关键词：

LIFE-SPAN EXTENSION; P70; S6; KINASE; TUBEROUS SCLEROSIS COMPLEX; MESSENGER-RNA TRANSLATION; CELL-GROWTH; MAMMALIAN TARGET; PROTEIN-KINASE; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; AMINO-ACIDS;

D O I：

10.1038/nrm3025

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.

引用

收藏

页码：21 / 35

页数：15

相关论文

共 175 条

[11] A Ras Signaling Complex Controls the RasC-TORC2 Pathway and Directed Cell Migration [J].

Charest, Pascale G. ;

Shen, Zhouxin ;

Lakoduk, Ashley ;

Sasaki, Atsuo T. ;

Briggs, Steven P. ;

Firtel, Richard A. .

DEVELOPMENTAL CELL, 2010, 18 (05) :737-749

[12] mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells [J].

Chen, Chong ;

Liu, Yu ;

Liu, Yang ;

Zheng, Pan .

SCIENCE SIGNALING, 2009, 2 (98) :ra75

[13] Dual Inhibition of Class IA Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin as a New Therapeutic Option for T-Cell Acute Lymphoblastic Leukemia [J].

Chiarini, Francesca ;

Fala, Federica ;

Tazzari, Pier Luigi ;

Ricci, Francesca ;

Astolfi, Annalisa ;

Pession, Andrea ;

Pagliaro, Pasqualepaolo ;

McCubrey, James A. ;

Martelli, Alberto M. .

CANCER RESEARCH, 2009, 69 (08) :3520-3528

[14] Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation [J].

Choo, Andrew Y. ;

Yoon, Sang-Oh ;

Kim, Sang Gyun ;

Roux, Philippe P. ;

Blenis, John .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (45) :17414-17419

[15] AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity [J].

Chresta, Christine M. ;

Davies, Barry R. ;

Hickson, Ian ;

Harding, Tom ;

Cosulich, Sabina ;

Critchlow, Susan E. ;

Vincent, John P. ;

Ellston, Rebecca ;

Jones, Darren ;

Sini, Patrizia ;

James, Dominic ;

Howard, Zoe ;

Dudley, Phillippa ;

Hughes, Gareth ;

Smith, Lisa ;

Maguire, Sharon ;

Hummersone, Marc ;

Malagu, Karine ;

Menear, Keith ;

Jenkins, Richard ;

Jacobsen, Matt ;

Smith, Graeme C. M. ;

Guichard, Sylvie ;

Pass, Martin .

CANCER RESEARCH, 2010, 70 (01) :288-298

[16] Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner [J].

Christie, GR ;

Hajduch, E ;

Hundal, HS ;

Proud, CG ;

Taylor, PM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (12) :9952-9957

[17] Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to the promoter but does not participate in alteration of the number of active genes [J].

Claypool, JA ;

French, SL ;

Johzuka, K ;

Eliason, K ;

Vu, L ;

Dodd, JA ;

Beyer, AL ;

Nomura, M .

MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (02) :946-956

[18] Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome [J].

Corradetti, MN ;

Inoki, K ;

Bardeesy, N ;

DePinho, RA ;

Guan, KL .

GENES & DEVELOPMENT, 2004, 18 (13) :1533-1538

[19] Hypothalamic mTOR signaling regulates food intake [J].

Cota, D ;

Proulx, K ;

Smith, KAB ;

Kozma, SC ;

Thomas, G ;

Woods, SC ;

Seeley, RJ .

SCIENCE, 2006, 312 (5775) :927-930

[20] INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].

CROSS, DAE ;

ALESSI, DR ;

COHEN, P ;

ANDJELKOVICH, M ;

HEMMINGS, BA .

NATURE, 1995, 378 (6559) :785-789

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