Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression.
Cell growth (an increase in cell mass and size through macromolecular biosynthesis) and cell cycle progression are generally tightly coupled, allowing cells to proliferate continuously while maintaining their size. The target of rapamycin (TOR) is an evolutionarily conserved kinase that integrates signals from nutrients (amino acids and energy) and growth factors (in higher eukaryotes) to regulate cell growth and cell cycle progression coordinately. In mammals, TOR is best known to regulate translation through the ribosomal protein S6 kinases (S6Ks) and the eukaryotic translation initiation factor 4E-binding proteins. Consistent with the contribution of translation to growth, TOR regulates cell, organ, and organismal size. The identification of the tumor suppressor proteins tuberous sclerosis1 and 2 (TSC1 and 2) and Ras-homolog enriched in brain (Rheb) has biochemically linked the TOR and phosphatidylinositol 3-kinase (PI3K) pathways, providing a mechanism for the crosstalk that occurs between these pathways. 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. Not only may inhibition of TOR be effective in cancer treatment, but rapamycin is an FDA-approved immunosuppressive and cardiology drug. We review here what is known (and not known) about the function of TOR in cellular and animal physiology.
Fingar
Diane C
DC
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA.
Blenis
John
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D009369:Neoplasms / Q000209:etiology; D009479:Neuropeptides / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020559:Monomeric GTP-Binding Proteins; D009479:Neuropeptides; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011494:Protein Kinases; D011506:Proteins; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C087000:EIF4EBP1 protein, human; C490211:RHEB protein, human; C000624650:TSC1 protein, human; C546842:MTOR protein, human