Rapamycin regulates biochemical metabolites

Paola Tucci, Giovanni Porta, Massimiliano Agostini, Alexey Antonov, Alexander Vasilievich Garabadgiu, Gerry Melino, Anne E. Willis

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2454-2467
Number of pages14
JournalCell Cycle
Volume12
Issue number15
DOIs
Publication statusPublished - Aug 1 2013

Keywords

  • Autophagy
  • Cell death
  • MEF
  • Metabolism
  • MTOR
  • P53 family
  • P73
  • Rapamycin

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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