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Quantitative Phosphoproteomics Reveal mTORC1 Activates de Novo Pyrimidine Synthesis

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Science  15 Mar 2013:
Vol. 339, Issue 6125, pp. 1320-1323
DOI: 10.1126/science.1228771

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Coordinating Metabolism

Growth factors help to coordinate metabolism with growth in part by stimulating the activity of the protein kinase mTORC1 (mechanistic target of rapamycin complex 1). Ben-Sahra et al. (p. 1323, published online 21 February) and Robitaille et al. (p. 1320, published online 21 February) independently identified a key target of mTORC1—carbamolyl-phosphate synthase 2, or CAD, the rate-limiting enzyme for de novo synthesis of pyrimidines. Metabolomic profiling and phosphoproteomic analyses of normal cells and cells lacking signaling by mTORC1 converged on CAD as a key point at which growth-promoting signals also ramp up production of nucleic acids.

  • Corresponding author. E-mail: m.hall{at}unibas.ch