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Updated: May 8, 2026

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Published on: July 23, 2010
E2F1 activates p53 transcription through its distal site and participates in apoptosis induction in HPV-positive
Anthony Massip1, Tania Arcondéguy, Christian Touriol
1INSERM UMR 1037, Cancer Research Center of Toulouse (CRCT), Cancer Department, 1 Avenue Jean Poulhes, Toulouse, France.
Abstract:
The p53 tumor suppressor protein, one of the most extensively studied proteins, plays a pivotal role in cellular checkpoints that respond to DNA damage to prevent tumorigenesis. However, the transcriptional control of the p53 gene has not been fully characterized. We report that the transcription factor E2F1 binds only to the E2F1 distal site of the p53 promoter in the human papillomavirus positive carcinoma HeLa cell line. Moreover, we showed that etoposide, a DNA damaging agent, activates p53 transcription through the E2F1 pathway. This increase correlates with apoptosis induction as disruption of this pathway led to reduced apoptosis stimulation by the DNA damaging agent.
Insights
The transcription factor E2F1 activates p53 gene transcription in response to DNA damage, a pathway crucial for initiating apoptosis and preventing cancer. This finding clarifies a key aspect of p53 regulation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- The p53 protein is a critical tumor suppressor involved in DNA damage response.
- Transcriptional regulation of the p53 gene remains incompletely understood.
- Human papillomavirus-positive carcinoma cells provide a model for studying p53 regulation.
Purpose of the Study:
- To investigate the transcriptional control of the p53 gene.
- To identify transcription factors binding to the p53 promoter.
- To elucidate the role of the E2F1 pathway in p53 activation and apoptosis.
Main Methods:
- Utilized HeLa cell line (HPV-positive carcinoma).
- Analyzed transcription factor E2F1 binding to the p53 promoter.
- Investigated the effect of etoposide (DNA damaging agent) on p53 transcription.
- Assessed apoptosis induction and the impact of pathway disruption.
Main Results:
- E2F1 specifically binds to the distal E2F1 site of the p53 promoter in HeLa cells.
- Etoposide treatment activates p53 transcription via the E2F1 pathway.
- Disruption of the E2F1-p53 pathway significantly reduces etoposide-induced apoptosis.
Conclusions:
- The E2F1 transcription factor plays a significant role in regulating p53 gene expression following DNA damage.
- The E2F1-mediated activation of p53 is essential for triggering apoptosis in response to genotoxic stress.
- Understanding this pathway offers insights into cancer prevention mechanisms.
Related Concept Videos
Abnormal Proliferation
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DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
The Intrinsic Apoptotic Pathway
Mitogens and the Cell Cycle

