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Consistency test of the cell cycle: roles for p53 and EGR1

Yaara Zwang1, Moshe Oren, Yosef Yarden

  • 1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

Cancer Research
|February 9, 2012
PubMed

Insights

Mammalian cells possess a "consistency test" involving EGR1, AKT, and p53 to ignore brief mitogen signals. This mechanism prevents unnecessary cell division in normal cells but is often defective in cancer.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Cancer biology

Background:

  • Mammalian cells encounter numerous mitogens, necessitating mechanisms to filter irrelevant signals.
  • Cellular noise reduction is crucial for maintaining normal physiological processes and preventing uncontrolled proliferation.

Purpose of the Study:

  • To elucidate the molecular mechanisms of a noise-reduction filter in mammalian cells.
  • To investigate the roles of EGR1, AKT, and p53 in signal consistency assessment.
  • To explore the implications of this filter's dysfunction in cancer.

Main Methods:

  • Analysis of molecular pathways involved in signal processing.
  • Investigating the formation and regulation of p53-chromatin complexes.
  • Assessing the impact of mitogen presence duration on cellular responses.

Main Results:

  • Identified a noise-reduction filter involving Early Growth Response 1 (EGR1), AKT, and tumor protein p53.
  • Demonstrated that transient mitogen exposure leads to inhibitory p53-chromatin complexes.
  • Showed that these complexes are only resolved if the mitogen persists for an extended period.

Conclusions:

  • The identified "consistency test" ensures cell division only occurs upon sustained mitogenic stimulation, preventing aberrant cell cycles.
  • Defects in this consistency test may contribute to the uncontrolled cell proliferation observed in many cancer cells.

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