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Updated: Sep 14, 2025
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
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E2F activity determines mitosis versus whole-genome duplication in G2-arrested cells
Kibum Kim1, Jessica Armand1,2, Sungsoo Kim1,2
1Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Nature Communications
|July 21, 2025
Summary
Mitogenic signaling controls cell fate in G2 arrest, determining mitosis entry or whole-genome duplication. This pathway impacts cancer cell genome instability and aggressive behavior.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Biology
Background:
- Mitogenic signaling regulates G1 cell-cycle entry.
- The role of mitogenic signaling in the G2 phase is not well understood.
- Cell fate decisions in G2 arrest are critical for genomic stability.
Purpose of the Study:
- To investigate the function of mitogenic signaling in G2-arrested cells.
- To elucidate the molecular mechanisms by which mitogenic signals control cell fate in G2.
- To understand the implications of this pathway in cancer progression.
Main Methods:
- Studied G2-arrested cells under conditions of CDK4/6 and CDK2 suppression.
- Analyzed E2F transcriptional activity, c-Myc modulation, and APC/C inactivation.
- Investigated the CDK2-Rb feedback loop and FoxM1 phosphorylation.
- Examined the impact of this pathway on cell-cycle re-entry and whole-genome duplication.
Main Results:
- Mitogenic signaling modulates E2F activity via c-Myc in G2 arrest.
- E2F levels dictate APC/C inactivation status and the CDK2-Rb feedback loop.
- Maintaining APC/C inactivation promotes mitotic entry via CDK2 activation and FoxM1 phosphorylation.
- APC/C reactivation leads to whole-genome duplication, mirroring G1-phase processes.
Conclusions:
- A novel mitogen-dependent checkpoint in G2 phase controls cell fate.
- This pathway dictates whether G2-arrested cells enter mitosis or undergo whole-genome duplication.
- In cancer, this process contributes to genome instability, oncogene amplification, and aggressive behavior.
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