Journal ArticleDOI
Targeting mTOR signaling for cancer therapy.
Shile Huang,Peter J. Houghton +1 more
TLDR
Emerging results suggest that inhibition of mTOR signaling can be exploited as a potential tumour-selective therapeutic strategy.About:
This article is published in Current Opinion in Pharmacology.The article was published on 2003-08-01. It has received 455 citations till now. The article focuses on the topics: RPTOR & PI3K/AKT/mTOR pathway.read more
Citations
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Journal ArticleDOI
Development by Self-Digestion: Molecular Mechanisms and Biological Functions of Autophagy
Beth Levine,Daniel J. Klionsky +1 more
TL;DR: This review summarizes the current knowledge about the molecular machinery of autophagy and the role of the autophagic machinery in eukaryotic development and identifies a set of evolutionarily conserved genes that are essential forAutophagy.
Journal ArticleDOI
Autophagy in cell death: an innocent convict?
Beth Levine,Junying Yuan +1 more
TL;DR: The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death, but this concept has now been evaluated using cells and organisms deficient in Autophagy genes to indicate that, at least in cells with intact apoptotic machinery, it is primarily a pro-survival rather than aPro-death mechanism.
Journal ArticleDOI
Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression
Diane C. Fingar,John Blenis +1 more
TL;DR: TOR is emerging as a novel antitumor target, since the TOR inhibitor rapamycin appears to be effective against tumors resulting from aberrantly high PI3K signaling.
Journal ArticleDOI
Dysregulation of the TSC-mTOR pathway in human disease.
TL;DR: Emerging evidence for a functional relationship between the mTOR signaling pathway and several genetic diseases is discussed, and evidence supporting a model in which dysregulation of mTOR may be a common molecular basis for hamartoma syndromes and for other cellular hypertrophic disorders is presented.
Journal ArticleDOI
Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy.
Hans-Guido Wendel,Elisa de Stanchina,Jordan S. Fridman,Jordan S. Fridman,Abba Malina,Sagarika Ray,Scott C. Kogan,Carlos Cordon-Cardo,Jerry Pelletier,Scott W. Lowe +9 more
TL;DR: It is shown that Akt promotes tumorigenesis and drug resistance by disrupting apoptosis, and that disruption of Akt signalling using the mTOR inhibitor rapamycin reverses chemoresistance in lymphomas expressing Akt, but not in those with other apoptotic defects.
References
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Journal ArticleDOI
mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery
Do Hyung Kim,Dos D. Sarbassov,Siraj M. Ali,Jessie E. King,Robert R. Latek,Hediye Erdjument-Bromage,Paul Tempst,David M. Sabatini +7 more
TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.
Journal ArticleDOI
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
Journal ArticleDOI
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Eric J. Brown,Mark W. Albers,Tae Bum Shin,Kazuo ichikawa,Curtis Keith,William S. Lane,Stuart L. Schreiber +6 more
TL;DR: A mammalian FKBP–rapamycin-associated protein (FRAP) is isolate whose binding to structural variants of rapamycin complexed to FK BP12 correlates with the ability of these ligands to inhibit cell-cycle progression.
Journal ArticleDOI
Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control
Robbie Loewith,Estela Jacinto,Stephan Wullschleger,Anja Lorberg,José L. Crespo,Debora Bonenfant,Wolfgang Oppliger,Paul Jenoe,Michael N. Hall +8 more
TL;DR: Two functionally distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling.
Journal ArticleDOI
Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
Kenta Hara,Yoshiko Maruki,Xiaomeng Long,Ken-ichi Yoshino,Noriko Oshiro,Sujuti Hidayat,Chiharu Tokunaga,Joseph Avruch,Kazuyoshi Yonezawa +8 more
TL;DR: Raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo and yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR.
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