Mammalian TOR: a homeostatic ATP sensor.
The bacterial macrolide rapamycin is an efficacious anticancer agent against solid tumors. In a hypoxic environment, the increase in mass of solid tumors is dependent on the recruitment of mitogens and nutrients. When nutrient concentrations change, particularly those of essential amino acids, the mammalian Target of Rapamycin (mTOR) functions in regulatory pathways that control ribosome biogenesis and cell growth. In bacteria, ribosome biogenesis is independently regulated by amino acids and adenosine triphosphate (ATP). Here we demonstrate that the mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and that mTOR itself is an ATP sensor.
Dennis
P B
PB
The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Jaeschke
A
A
Saitoh
M
M
Fowler
B
B
Kozma
S C
SC
Thomas
G
G
D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003847:Deoxyglucose / Q000494:pharmacology; D004789:Enzyme Activation; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin
D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D000730:Androstadienes; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D007328:Insulin; D010750:Phosphoproteins; D012346:RNA, Transfer, Amino Acyl; D011993:Recombinant Fusion Proteins; D012402:Rotenone; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D011494:Protein Kinases; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000077191:Wortmannin