Related Experiment Video
Updated: Jun 28, 2026

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
Published on: November 22, 2017
mTOR regulates autophagy-associated genes downstream of p73
Jennifer M Rosenbluth1, Jennifer A Pietenpol
1Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Abstract:
The p53 family consists of three transcription factors, p53, p63 and p73 that share domain architecture and sequence identity. The mTOR (mammalian target of rapamycin) kinase responds to growth factors and nutrient levels to regulate cellular growth and autophagy. Whereas p53 acts both upstream and downstream of mTOR, gene signature-based analyses have revealed that p73 is inhibited by mTOR activity. p53 can both activate and repress autophagy levels depending on cellular context. While less is known about p73, recent studies have shown that it induces cellular autophagy and multiple autophagy-associated genes downstream of mTOR. Chromatin immunoprecipitation analyses demonstrate that endogenous p73 binds the regulatory regions of genes such as ATG5, ATG7 and UVRAG. How p73 regulates the expression levels of these genes in response to different cellular stresses remains unknown. Because p53 family members play key roles in tumor suppression, development, aging and neurodegeneration, the context and manner by which these transcription factors regulate autophagy may have implications for a wide range of human diseases.
Insights
The p73 protein, part of the p53 family, induces autophagy and targets autophagy-related genes. Its regulation by mammalian target of rapamycin (mTOR) and cellular stress requires further investigation for disease implications.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- The p53 family, including p53, p63, and p73, comprises transcription factors with shared structural and sequence characteristics.
- Mammalian target of rapamycin (mTOR) kinase regulates cellular growth and autophagy in response to nutrients and growth factors.
- While p53's role in autophagy is context-dependent, p73's function is less understood, though recent studies suggest it induces autophagy.
Purpose of the Study:
- To investigate the role of p73 in regulating autophagy and autophagy-associated genes.
- To explore the relationship between p73, mTOR signaling, and cellular stress responses.
- To elucidate the mechanisms by which p73 controls autophagy gene expression.
Main Methods:
- Gene signature-based analyses to assess mTOR activity effects on p73.
- Chromatin immunoprecipitation (ChIP) to identify p73 binding sites on autophagy-related genes (e.g., ATG5, ATG7, UVRAG).
Main Results:
- Gene signature analyses indicate mTOR activity inhibits p73.
- p73 induces cellular autophagy and upregulates multiple autophagy-associated genes downstream of mTOR.
- ChIP assays confirm endogenous p73 binding to regulatory regions of key autophagy genes like ATG5, ATG7, and UVRAG.
Conclusions:
- p73 actively induces autophagy and regulates critical autophagy genes, particularly downstream of mTOR.
- The precise mechanisms of p73-mediated gene regulation under cellular stress remain to be elucidated.
- Understanding p73's regulation of autophagy is crucial given the p53 family's involvement in tumor suppression, aging, and neurodegeneration.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
Abnormal Proliferation
Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
