Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1.

Article Details

Citation

Ben-Sahra I, Howell JJ, Asara JM, Manning BD

Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1.

Science. 2013 Mar 15;339(6125):1323-8. doi: 10.1126/science.1228792. Epub 2013 Feb 21.

PubMed ID
23429703 [ View in PubMed
]
Abstract

Cellular growth signals stimulate anabolic processes. The mechanistic target of rapamycin complex 1 (mTORC1) is a protein kinase that senses growth signals to regulate anabolic growth and proliferation. Activation of mTORC1 led to the acute stimulation of metabolic flux through the de novo pyrimidine synthesis pathway. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. Growth signaling through mTORC1 thus stimulates the production of new nucleotides to accommodate an increase in RNA and DNA synthesis needed for ribosome biogenesis and anabolic growth.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
CAD proteinP27708Details
Serine/threonine-protein kinase mTORP42345Details