Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1

TLDR

mTORC1 coordinates metabolism and growth by stimulating CAD, the rate‑limiting enzyme of de novo pyrimidine synthesis. Metabolomic and phosphoproteomic profiling of cells with and without mTORC1 signaling identified CAD as the key node where growth signals upregulate nucleic acid production. Ben‑Sahra et al.

Abstract

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.