Cited by 525PI3K/AKT/mTOR signaling in cancerBiochemical and Molecular ResearchProtein Kinase Regulation and GTPase Signaling

Quantitative Phosphoproteomics Reveal mTORC1 Activates de Novo Pyrimidine Synthesis

Open access
Robitaille, Aaron M., Christen, Stefan, Shimobayashi, Mitsugu, Cornu, Marion, Fava, Luca L., Moes, Suzette, Prescianotto-Baschong, Cristina, Sauer, Uwe +2 more·2013·Science

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.

Integrity signals

Registry

Crossref · 10.1126/science.1228771

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Glutamine-induced activation of mTORC1 results in phosphorylation of CAD, which catalyzes the condensation reaction converting glutamine-derived nitrogen into the pyrimidine precursor orotate.

    “Moreover, glutamine-induced activation of mTORC1 results in the phosphorylation of the enzyme complex called carbamoyl phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), which catalyzes the condensation reaction converting glutamine-derived nitrogen into the pyrimidine precursor orotate34,35.”

    From Glutamine reliance in cell metabolism (2020) · cites this paper as [35]

  • CAD activity is regulated via phosphorylation by MAPK and by mTORC1-dependent S6 kinase.

    “Furthermore, activity of CAD enzyme is regulated via phosphorylation by MAPK and by mTORC1-dependent S6 kinase (Ben-Sahra et al., 2013; Graves et al., 2000; Robitaille et al., 2013).”

    From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Robitaille et al., 2013

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Robitaille, A. M., Christen, S., Shimobayashi, M., Cornu, M., Fava, L. L., Moes, S., Prescianotto-Baschong, C., Sauer, U., Jenoe, P., & Hall, M. N.
Affiliations
  • University of Basel (CH)
  • ETH Zurich (CH)
  • Biozentrum, University of Basel, 4056 Basel, Switzerland.
Corresponding author
  • Fava, Luca L.
  • Hall, Michael N.
Venue
Science
Published
2013-03-15
Volume
339
Issue
6125
Pages
1320-1323
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2057650061
Cited by
525
References
42
Citations by year
2026: 30 · 2025: 33 · 2024: 26 · 2023: 32 · 2022: 45 · 2021: 50 · 2020: 43 · 2019: 37 · 2018: 38 · 2017: 46 · 2016: 39 · 2015: 46 · 2014: 38 · 2013: 22
FWCI
21.52
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • edoc (University of Basel) (acceptedVersion)
  • Iris (University of Trento) (submittedVersion)
  • edoc (University of Basel)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
mTORC1, de novo pyrimidine biosynthesis, aspartate transcarbamylase, dihydroorotase, S6 kinase, protein phosphorylation, S phase progression, nucleotide synthesis, cell proliferation
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Animals, Aspartate Carbamoyltransferase, Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing), Cells, Cultured, Dihydroorotase, HeLa Cells, Humans, Phosphoproteins, Pyrimidines, Mice, Knockout, Proteome, Multiprotein Complexes, Mice, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review