Molecular mechanisms of mTOR-mediated translational control

被引:2027
作者
Ma, Xiaoju Max [1 ]
Blenis, John [2 ]
机构
[1] Genentech Inc, Dept Res Oncol Diagnost, San Francisco, CA 94080 USA
[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
关键词
MESSENGER-RNA TRANSLATION; ACTIVATED PROTEIN-KINASE; INITIATION-FACTOR; 4E; KAPPA-B-KINASE; SPLICING FACTOR SF2/ASF; RICH AKT SUBSTRATE; 40 KDA PRAS40; TUBEROUS-SCLEROSIS; MAMMALIAN TARGET; CELL-GROWTH;
D O I
10.1038/nrm2672
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The process of translation requires substantial cellular resources. Cells have therefore evolved complex mechanisms to control overall protein synthesis as well as the translation of specific mRNAs that are crucial for cell growth and proliferation. At the heart of this process is the mammalian target of rapamycin (mTOR) signalling pathway, which senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis. Here, we highlight recent findings on the regulators and effectors of mTOR and discuss specific cases that serve as paradigms for the different modes of mTOR regulation and its control of translation.
引用
收藏
页码:307 / 318
页数:12
相关论文
共 123 条
[1]   A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets [J].
Arsham, AM ;
Howell, JJ ;
Simon, MC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (32) :29655-29660
[2]   Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors [J].
Ballif, BA ;
Roux, PP ;
Gerber, SA ;
MacKeigan, JP ;
Blenis, J ;
Gygi, SP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (03) :667-672
[3]   The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation [J].
Beuvink, I ;
Boulay, A ;
Fumagalli, S ;
Zilbermann, F ;
Ruetz, S ;
O'Reilly, T ;
Natt, F ;
Hall, J ;
Lane, HA ;
Thomas, G .
CELL, 2005, 120 (06) :747-759
[4]   Regulation of peptide-chain elongation in mammalian cells [J].
Browne, GJ ;
Proud, CG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2002, 269 (22) :5360-5368
[5]   Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning [J].
Cai, SL ;
Tee, AR ;
Short, JD ;
Bergeron, JM ;
Kim, J ;
Shen, JJ ;
Guo, RF ;
Johnson, CL ;
Kiguchi, K ;
Walker, CL .
JOURNAL OF CELL BIOLOGY, 2006, 173 (02) :279-289
[6]   Translational control of gene expression and disease [J].
Calkhoven, CF ;
Müller, C ;
Leutz, A .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (12) :577-583
[7]   The RSK factors of activating the Ras/MAPK signaling cascade [J].
Carriere, Audrey ;
Ray, Hind ;
Blenis, John ;
Roux, Philippe P. .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2008, 13 :4258-4275
[8]   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
[9]   Translational control: the cancer connection [J].
Clemens, MJ ;
Bommer, UA .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1999, 31 (01) :1-23
[10]   TOR kinase homologs function in a signal transduction pathway that is conserved from yeast to mammals [J].
Cutler, NS ;
Heitman, J ;
Cardenas, ME .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1999, 155 (1-2) :135-142