The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell growth and metabolism. Leucine (Leu) activates mTORC1 and many have tried to identify the mechanisms whereby cells sense Leu in this context. Here we describe that the Leu metabolite acetyl-coenzyme A (AcCoA) positively regulates mTORC1 activity by EP300-mediated acetylation of the mTORC1 regulator, Raptor, at K1097. Leu metabolism and consequent mTORC1 activity are regulated by intermediary enzymes. As AcCoA is a Leu metabolite, this process directly correlates with Leu abundance, and does not require Leu sensing via intermediary proteins, as has been described previously. Importantly, we describe that this pathway regulates mTORC1 in a cell-type-specific manner. Finally, we observed decreased acetylated Raptor, and inhibited mTORC1 and EP300 activity in fasted mice tissues. These results provide a direct mechanism for mTORC1 regulation by Leu metabolism.
Pubmed ID: 30197302 RIS Download
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsThis polyclonal targets Full length recombinant GFP
View all literature mentionsThis polyclonal targets Phospho-ULK1 (Ser757)
View all literature mentionsThis polyclonal targets ULK1
View all literature mentionsThis unknown targets mTOR, phospho (Ser2481)
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein, phospho (Ser235 / Ser236)
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
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View all literature mentionsThis polyclonal targets Phospho-Raptor (Ser792)
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View all literature mentionsThis monoclonal targets p70 S6 Kinase, phospho (Thr389)
View all literature mentionsThis polyclonal targets p70 S6 Kinase
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View all literature mentionsThis polyclonal targets Phospho-ATP-Citrate Lyase (Ser455)
View all literature mentionsThis polyclonal targets Acly
View all literature mentionsThis monoclonal targets Atg7 (D12B11) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets Actin
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View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsThis polyclonal targets KIAA1303
View all literature mentionsThis polyclonal targets Full length recombinant GFP
View all literature mentionsThis monoclonal targets p300 CT
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis polyclonal targets Acetylated-Lysine
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets 4E-BP1
View all literature mentionsThis monoclonal targets Acetylated-Lysine (Ac-K2-100) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-ATP-Citrate Lyase (Ser455)
View all literature mentionsThis monoclonal targets Atg7 (D12B11) Rabbit mAb
View all literature mentionsThis polyclonal targets Acly
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets p70 S6 Kinase, phospho (Thr389)
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View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis monoclonal targets PRAS40
View all literature mentionsThis monoclonal targets LAMP1
View all literature mentionsThis monoclonal targets G L (86B8) Rabbit mAb
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis monoclonal targets LAMTOR1/C11orf59 (D11H6) XP Rabbit mAb
View all literature mentionsThis unknown targets HA Epitope Tag
View all literature mentionsThis unknown targets
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View all literature mentionsThis monoclonal targets Raptor (24C12) Rabbit mAb
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis polyclonal targets Phospho-ULK1 (Ser757)
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein, phospho (Ser235 / Ser236)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis unknown targets mTOR, phospho (Ser2481)
View all literature mentionsThis monoclonal targets RagA (D8B5) Rabbit mAb
View all literature mentionsThis polyclonal targets PRKCA
View all literature mentionsThis polyclonal targets Phospho-Raptor (Ser792)
View all literature mentionsThis monoclonal targets RagC
View all literature mentionsThis monoclonal targets RagB (D18F3) Rabbit mAb
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