PMID- 23839040 OWN - NLM STAT- MEDLINE DCOM- 20140422 LR - 20220129 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 12 IP - 15 DP - 2013 Aug 1 TI - Rapamycin regulates biochemical metabolites. PG - 2454-67 LID - 10.4161/cc.25450 [doi] AB - The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73(-/-) were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73(-/-) cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. FAU - Tucci, Paola AU - Tucci P AD - Medical Research Council; Toxicology Unit; Leicester, UK; Department of Pharmacy, Health and Nutritional Sciences; University of Calabria; Rende, Cosenza, Italy. FAU - Porta, Giovanni AU - Porta G FAU - Agostini, Massimiliano AU - Agostini M FAU - Antonov, Alexey AU - Antonov A FAU - Garabadgiu, Alexander Vasilievich AU - Garabadgiu AV FAU - Melino, Gerry AU - Melino G FAU - Willis, Anne E AU - Willis AE LA - eng GR - GGP09133/TI_/Telethon/Italy GR - MC_U132670600/MRC_/Medical Research Council/United Kingdom GR - MC_UP_A600_1023/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130628 PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (Nuclear Proteins) RN - 0 (delta Np73, mouse) RN - AE28F7PNPL (Methionine) RN - GAN16C9B8O (Glutathione) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Biosynthetic Pathways/drug effects MH - Cells, Cultured MH - Glutathione/biosynthesis MH - Glycolysis/drug effects MH - Metabolome/*drug effects MH - Methionine/metabolism MH - Mice MH - Mice, Knockout MH - Nuclear Proteins/genetics/metabolism MH - Pentose Phosphate Pathway/drug effects MH - Sirolimus/*pharmacology PMC - PMC3841324 OTO - NOTNLM OT - MEF OT - autophagy OT - cell death OT - mTOR OT - metabolism OT - p53 family OT - p73 OT - rapamycin EDAT- 2013/07/11 06:00 MHDA- 2014/04/23 06:00 PMCR- 2013/06/28 CRDT- 2013/07/11 06:00 PHST- 2013/07/11 06:00 [entrez] PHST- 2013/07/11 06:00 [pubmed] PHST- 2014/04/23 06:00 [medline] PHST- 2013/06/28 00:00 [pmc-release] AID - 25450 [pii] AID - 2013CC4988R [pii] AID - 10.4161/cc.25450 [doi] PST - ppublish SO - Cell Cycle. 2013 Aug 1;12(15):2454-67. doi: 10.4161/cc.25450. Epub 2013 Jun 28.