Rapamycin regulates biochemical metabolites..pdf (3.04 MB)
Download file

Rapamycin regulates biochemical metabolites.

Download (3.04 MB)
journal contribution
posted on 21.03.2017, 11:57 by Paola Tucci, Giovanni Porta, Massimiliano Agostini, Alexey Antonov, Alexander Vasilievich Garabadgiu, Gerry Melino, Anne E. Willis
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.

Funding

This work has been supported by the Medical Research Council, UK; grants from “Alleanza contro il Cancro” (ACC12), MIUR/ PRIN (20078P7T3K_001)/FIRB (RBIP06LCA9_0023, RBIP06LCA9_0C), AIRC (2008-2010_33-08) (#5471) (2011- IG11955), AIRC 5xmille (#9979), Italian Human ProteomeNet RBRN07BMCT, MIUR/PRIN (2008MRLSNZ_004), Telethon Grant (GGPO9133), to GM Research described in this article was also supported in part by Min. Salute (Ricerca oncologica 26/07) and IDI-IRCCS (RF06 c.73, RF07 c.57, RF08 c.15, RF07 c.57) to GM. Work was supported by Ministry of Education and Science of the Russian Federation (11.G34.31.0069).

History

Citation

Cell Cycle, 2013, 12 (15), pp. 2454-2467

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biology

Version

AM (Accepted Manuscript)

Published in

Cell Cycle

Publisher

Taylor & Francis

issn

1538-4101

eissn

1551-4005

Acceptance date

18/06/2013

Copyright date

2013

Available date

21/03/2017

Publisher version

http://www.tandfonline.com/doi/abs/10.4161/cc.25450

Notes

Supplemental materials may be found here: www.landesbioscience.com/journals/cc/article/25450

Language

en