Mammalian TOR: a homeostatic ATP sensor

PB Dennis, A Jaeschke, M Saitoh, B Fowler, SC Kozma… - Science, 2001 - science.org
PB Dennis, A Jaeschke, M Saitoh, B Fowler, SC Kozma, G Thomas
Science, 2001science.org
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) …
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.
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