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Related Experiment Video

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Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Rapamycin regulates biochemical metabolites.

Paola Tucci¹, Giovanni Porta, Massimiliano Agostini

¹Medical Research Council; Toxicology Unit; Leicester, UK; Department of Pharmacy, Health and Nutritional Sciences; University of Calabria; Rende, Cosenza, Italy.

Cell Cycle (Georgetown, Tex.)

|July 11, 2013

Summary

The mammalian target of rapamycin (mTOR) pathway regulates cell growth and is linked to cancer. This study investigated metabolic changes upon mTOR inhibition and the role of p73, revealing significant alterations in cellular stress response metabolites.

Keywords:

MEF autophagy cell death mTOR metabolism p53 family p73 rapamycin

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Area of Science:

Cellular Biology
Metabolomics
Molecular Oncology

Background:

The mammalian target of rapamycin (mTOR) pathway is crucial for protein synthesis, nutrient sensing, and cell growth.
Deregulation of the mTOR pathway is implicated in tumorigenesis.
p53 and its family member p73 interact with mTOR pathways via transcriptional regulation.

Purpose of the Study:

To investigate metabolic alterations in response to mTOR pathway inhibition.
To elucidate the role of the p73 protein in the cellular response to mTOR inhibition.

Main Methods:

Primary mouse embryonic fibroblasts from control and TAp73(-/-) mice were treated with rapamycin.
Global metabolome profiling was performed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS).

Main Results:

A rapamycin-dependent global metabolome profile was generated.
289 metabolites were identified, with 39 biochemical metabolites significantly altered.
Many altered metabolites are associated with cellular stress responses.

Conclusions:

mTOR inhibition profoundly impacts cellular metabolism.
p73 plays a role in mediating metabolic changes induced by mTOR inhibition.
These findings highlight the interplay between mTOR, p73, and cellular metabolism in the context of stress response.