{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Linder SJ"],"funding":["NIEHS NIH HHS","National Institute of Health","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["2131-2147"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11639397"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(12)"],"pubmed_abstract":["Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood. Here, using an unbiased screen, we identify ALDH18A1, which encodes P5CS, the rate-limiting enzyme in the proline biosynthetic pathway, as a gene that cells can downregulate in response to glutamine starvation. Notably, P5CS downregulation promotes de novo glutamine synthesis, highlighting a previously unrecognized metabolic plasticity of cancer cells. The glutamate conserved from reducing proline synthesis allows cells"],"journal":["Nature metabolism"],"pubmed_title":["Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells."],"pmcid":["PMC11639397"],"funding_grant_id":["P30 CA046934","R01 GM120109","R01 CA226871","R01 GM128448","F31 CA210310","R01 CA117907","R33 ES025638"],"pubmed_authors":["Martinez-Pastor B","Ferrer CM","Massri R","Galbraith MD","Kim E","Silveira GG","Espinosa JM","Lewis CA","Boon R","Gottlieb E","Rueda BR","Bernasocchi T","Ross KN","Matoba Y","Linder SJ","Sullivan KD","Cho HM","Vidoudez C","Shroff S","Oliveira-Costa JP","Stott SL","Mostoslavsky R"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of the proline metabolism rate-limiting enzyme P5CS allows proliferation of glutamine-restricted cancer cells.","description":"Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood. Here, using an unbiased screen, we identify ALDH18A1, which encodes P5CS, the rate-limiting enzyme in the proline biosynthetic pathway, as a gene that cells can downregulate in response to glutamine starvation. Notably, P5CS downregulation promotes de novo glutamine synthesis, highlighting a previously unrecognized metabolic plasticity of cancer cells. The glutamate conserved from reducing proline synthesis allows cells","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-03T23:25:59.026Z","creation":"2025-04-03T23:25:59.026Z"},"accession":"S-EPMC11639397","cross_references":{"pubmed":["37957387"],"doi":["10.1038/s42255-023-00919-3"]}}