Abstract：
:Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis. We find that the mTORC1 pathway is responsive to changes in purine nucleotides in a manner analogous to its sensing of amino acids. Depletion of cellular purines, but not pyrimidines, inhibits mTORC1, and restoration of intracellular adenine nucleotides via addition of exogenous purine nucleobases or nucleosides acutely reactivates mTORC1. Adenylate sensing by mTORC1 is dependent on the tuberous sclerosis complex (TSC) protein complex and its regulation of Rheb upstream of mTORC1, but independent of energy stress and AMP-activated protein kinase (AMPK). Even though mTORC1 signaling is not acutely sensitive to changes in intracellular guanylates, long-term depletion of guanylates decreases Rheb protein levels. Our findings suggest that nucleotide sensing, like amino acid sensing, enables mTORC1 to tightly coordinate nutrient availability with the synthesis of macromolecules, such as protein and nucleic acids, produced from those nutrients.
journal_name
Cell Repjournal_title
Cell reportsauthors
Hoxhaj G,Hughes-Hallett J,Timson RC,Ilagan E,Yuan M,Asara JM,Ben-Sahra I,Manning BDdoi
10.1016/j.celrep.2017.10.029subject
Has Abstractpub_date
2017-10-31 00:00:00pages
1331-1346issue
5issn
2211-1247pii
S2211-1247(17)31461-4journal_volume
21pub_type
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