Onset of Quiescence Following p53 Mediated Down-Regulation of H2AX in Normal Cells
2011

How p53 Regulates Cell Quiescence and Immortality through H2AX

publication 10 minutes Evidence: moderate

Author Information

Author(s): Atsumi Yuko, Fujimori Hiroaki, Fukuda Hirokazu, Inase Aki, Shinohe Keitaro, Yoshioka Yoshiko, Shikanai Mima, Ichijima Yosuke, Unno Junya, Mizutani Shuki, Tsuchiya Naoto, Hippo Yoshitaka, Nakagama Hitoshi, Masutani Mitsuko, Teraoka Hirobumi, Yoshioka Ken-ichi

Primary Institution: National Cancer Center Research Institute, Tokyo, Japan

Hypothesis

Normal cells regulate homeostasis preservation and abrogation through p53-mediated down-regulation of H2AX.

Conclusion

The study shows that down-regulation of H2AX by p53 helps maintain quiescence in normal cells, while its loss under growth stimulation leads to tetraploidization and immortality.

Supporting Evidence

  • Normal cells can become quiescent by down-regulating H2AX under p53 regulation.
  • Tetraploidization occurs in cells under continuous growth stimulation, leading to genomic instability.
  • Cells that maintain diploidy and low H2AX levels do not develop immortality.
  • H2AX levels are significantly reduced in quiescent cells compared to actively growing cells.
  • p53 plays a critical role in regulating H2AX levels to maintain cellular homeostasis.

Takeaway

This study found that when cells are not growing too fast, they can stay healthy and stable by lowering a protein called H2AX, but if they grow too quickly, they can become unstable and immortal.

Methodology

The study involved culturing mouse embryonic fibroblasts under different growth conditions to observe the effects of H2AX levels on cell quiescence and immortality.

Limitations

The study primarily focuses on mouse embryonic fibroblasts, which may not fully represent human cellular behavior.

Participant Demographics

The study used mouse embryonic fibroblasts (MEFs) and normal human fibroblasts (NHFs).

Digital Object Identifier (DOI)

10.1371/journal.pone.0023432

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