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

Issam Ben‐Sahra; Jessica J. Howell; John M. Asara; Brendan D. Manning

doi:10.1126/science.1228792

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.

Keywords

mTORC1P70-S6 Kinase 1PI3K/AKT/mTOR pathwayCell growthPyrimidine metabolismBiologyBiochemistryMetabolismCell biologyMechanistic target of rapamycinEnzymeStimulationDe novo synthesisKinaseSignal transductionChemistryNeuroscience

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Publication Info

Year: 2013
Type: article
Volume: 339
Issue: 6125
Pages: 1323-1328
Citations: 705
Access: Closed

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APA Style

                            
                                
                                    Issam Ben‐Sahra, 
                                
                                    Jessica J. Howell, 
                                
                                    John M. Asara
                                
                                et al.
                            
                            (2013). 
                            Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1. 
                            Science
                            , 339
                            (6125)
                            , 1323-1328.
                            https://doi.org/10.1126/science.1228792
                        

Identifiers

DOI: 10.1126/science.1228792