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Updated: Aug 11, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
14-3-3 proteins integrate E2F activity with the DNA damage response
Alasdair H Milton1, Nandkumar Khaire, Laura Ingram
1Laboratory of Cancer Biology, Division of Medical Sciences, University of Oxford, UK.
The EMBO Journal
|February 17, 2006
Summary
The study reveals that 14-3-3epsilon binds to DP-3, a subunit of E2F transcription factors. This interaction regulates cell cycle and apoptosis, integrating E2F activity with DNA damage responses.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The E2F family, crucial for regulating target genes, comprises E2F/DP heterodimers.
- DP-1 is a well-known E2F component, but DP-3 and its isoforms, including the nuclear localization signal (NLS), are less understood.
Purpose of the Study:
- To investigate the function of the DP-3 subunit, particularly its interaction with 14-3-3epsilon.
- To elucidate how this interaction influences E2F activity and cellular responses to DNA damage.
Main Methods:
- Investigated the binding site of 14-3-3epsilon within the DP-3 NLS region.
- Assessed the impact of 14-3-3epsilon binding on E2F-mediated cell cycle progression and apoptosis.
- Examined the role of DNA damage in controlling the DP-3 and 14-3-3epsilon interaction.
- Analyzed 14-3-3epsilon presence in E2F target gene promoter regions.
Main Results:
- Identified a 14-3-3epsilon binding site in the DP-3 NLS region.
- Demonstrated that 14-3-3epsilon binding modulates E2F's control over the cell cycle and apoptosis.
- Showed that the DP-3/14-3-3epsilon interaction is regulated by DNA damage.
- Found 14-3-3epsilon in promoters of E2F target genes, with its depletion inducing apoptosis.
Conclusions:
- DP-3, via its NLS, interacts with 14-3-3epsilon, providing a novel regulatory mechanism for E2F activity.
- The 14-3-3epsilon protein integrates E2F function with the cellular DNA damage response pathway, influencing cell fate.
- This interaction is critical for maintaining cellular homeostasis under genotoxic stress.
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