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Updated: May 9, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
TRP53 activates a global autophagy program to promote tumor suppression
Daniela Kenzelmann Broz1, Laura D Attardi
1Division of Radiation and Cancer Biology; Department of Radiation Oncology; Stanford University School of Medicine; Stanford, CA USA.
Abstract:
The mechanisms by which the TP53/TRP53 transcription factor acts as a tumor suppressor remain incompletely understood. To gain new insights into TP53/TRP53 biology, we used ChIP-seq and RNA-seq technologies to define global TRP53 transcriptional networks in primary cells subjected to DNA damage. Intriguingly, we identified a TRP53-regulated autophagy program, which can be coordinately regulated by the TRP53 family members TRP63 and TRP73 in certain settings. While autophagy is not involved in TRP53-dependent cell cycle arrest, it contributes to both TRP53-driven apoptosis in response to DNA damage and TRP53-mediated transformation suppression. Collectively, our genome-wide analyses reveal a profound role for TRP53 in regulating autophagy, through an extensive transcriptional network, and have demonstrated an important role for this program in promoting TRP53-mediated apoptosis and tumor suppression.
Insights
The tumor suppressor TP53 (tumor protein 53) regulates autophagy, a cellular process. This autophagy program is crucial for TP53-mediated apoptosis and tumor suppression following DNA damage.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The tumor suppressor function of the TP53 (tumor protein 53) transcription factor is critical for preventing cancer.
- However, the precise molecular mechanisms underlying TP53's tumor suppressor activity are not fully elucidated.
Purpose of the Study:
- To investigate the global transcriptional networks regulated by TP53 in response to DNA damage.
- To identify novel pathways and functions associated with TP53 in cellular processes.
Main Methods:
- Utilized ChIP-seq (Chromatin Immunoprecipitation sequencing) to map TP53 binding sites genome-wide.
- Employed RNA-seq (RNA sequencing) to analyze changes in gene expression profiles.
- Studied primary cells subjected to DNA damage to mimic cellular stress conditions.
Main Results:
- Identified a significant TP53-regulated autophagy program.
- Demonstrated that TP53 family members, TP63 and TP73, can also regulate this autophagy pathway.
- Found that autophagy is not involved in TP53-dependent cell cycle arrest but contributes to apoptosis and tumor suppression.
Conclusions:
- TP53 plays a profound role in regulating autophagy through an extensive transcriptional network.
- The identified autophagy program is essential for TP53-mediated apoptosis and tumor suppression.
- These findings provide new insights into TP53 biology and its function as a tumor suppressor.
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