The Complexes of Mammalian Target of Rapamycin

被引:124
作者
Zhou, Hongyu [1 ]
Huang, Shile [1 ,2 ]
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA
[2] Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71130 USA
关键词
Rapamycin; mTOR; S6K1; 4E-BP1; raptor; rictor; cancer; diabetes; ACTIVATED PROTEIN-KINASE; P70; S6; KINASE; RICH AKT SUBSTRATE; TUMOR-SUPPRESSOR PROTEINS; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; PEUTZ-JEGHERS-SYNDROME; RICTOR-MTOR COMPLEX; 40 KDA PRAS40; TUBEROUS-SCLEROSIS;
D O I
10.2174/138920310791824093
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mammalian target of rapamycin (mTOR) has attracted substantial attention because of its involvement in a variety of diseases, such as cancer, cardiac hypertrophy, diabetes and obesity. Current knowledge indicates that mTOR functions as two distinct multiprotein complexes, mTORC1 and mTORC2. mTORC1 phosphorylates p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and regulates cell growth, proliferation, and survival by integrating hormones, growth factors, nutrients, stressors and energy signals. In contrast, mTORC2 is insensitive to nutrients or energy conditions. However, in response to hormones or growth factors, mTORC2 phosphorylates Akt, and regulates actin cytoskeleton and cell survival. These findings not only reveal the crucial role of mTOR in physiology and pathology, but also reflect the complexity of the mTOR signaling network. In this review, we discuss the advances in studies of the mTOR complexes, including the interacting proteins, the upstream regulators and the downstream effectors of mTOR complexes, as well as their implication in certain human diseases.
引用
收藏
页码:409 / 424
页数:16
相关论文
共 225 条
[41]   Mammalian TOR: A homeostatic ATP sensor [J].
Dennis, PB ;
Jaeschke, A ;
Saitoh, M ;
Fowler, B ;
Kozma, SC ;
Thomas, G .
SCIENCE, 2001, 294 (5544) :1102-1105
[42]  
DILLING MB, 1994, CANCER RES, V54, P903
[43]   NEW ANTI-TUMOR SUBSTANCES OF NATURAL ORIGIN [J].
DOUROS, J ;
SUFFNESS, M .
CANCER TREATMENT REVIEWS, 1981, 8 (01) :63-87
[44]   Ribosomal S6 kinase signaling and the control of translation [J].
Dufner, A ;
Thomas, G .
EXPERIMENTAL CELL RESEARCH, 1999, 253 (01) :100-109
[45]   Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer [J].
Ekstrand, Anna Isinger ;
Jonsson, Mats ;
Lindblom, Annika ;
Borg, Ake ;
Nilbert, Mef .
FAMILIAL CANCER, 2010, 9 (02) :125-129
[46]   REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species [J].
Ellisen, LW ;
Ramsayer, KD ;
Johannessen, CM ;
Yang, A ;
Beppu, H ;
Minda, K ;
Oliner, JD ;
McKeon, F ;
Haber, DA .
MOLECULAR CELL, 2002, 10 (05) :995-1005
[47]   ACTIVITY OF RAPAMYCIN (AY-22,989) AGAINST TRANSPLANTED TUMORS [J].
ENG, CP ;
SEHGAL, SN ;
VEZINA, C .
JOURNAL OF ANTIBIOTICS, 1984, 37 (10) :1231-1237
[48]   Rho GTPases in cell biology [J].
Etienne-Manneville, S ;
Hall, A .
NATURE, 2002, 420 (6916) :629-635
[49]   A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma [J].
Fan, Qi-Wen ;
Knight, Zachary A. ;
Goldenberg, David D. ;
Yu, Wei ;
Mostov, Keith E. ;
Stokoe, David ;
Shokat, Kevan M. ;
Weiss, William A. .
CANCER CELL, 2006, 9 (05) :341-349
[50]   Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2 [J].
Feldman, Morris E. ;
Apsel, Beth ;
Uotila, Aino ;
Loewith, Robbie ;
Knight, Zachary A. ;
Ruggero, Davide ;
Shokat, Kevan M. .
PLOS BIOLOGY, 2009, 7 (02) :371-383