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Updated: Sep 14, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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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
PubMed

Insights

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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