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Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a

Ikuko Yokota1, Yasushi Sasaki, Lisa Kashima

  • 1Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.

International Journal of Oncology
|November 3, 2010
PubMed

Insights

The tumor suppressor p53 family directly regulates the early growth response 2 (EGR2) gene. EGR2 plays a role in p53-mediated apoptosis, a key process in cancer suppression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The tumor suppressor p53 is a crucial transcription factor involved in cellular stress response, inducing growth arrest and apoptosis.
  • While numerous p53-regulated genes have been identified, a definitive target gene essential for p53's apoptotic function remained elusive.
  • The p53 family, including p53, p63, and p73, plays vital roles in cellular processes and disease.

Purpose of the Study:

  • To identify novel direct transcriptional targets of the p53 family.
  • To investigate the role of identified targets in mediating p53-dependent apoptosis.
  • To elucidate the functional significance of early growth response 2 (EGR2) in the p53 pathway.

Main Methods:

  • Microarray analysis was employed to identify genes regulated by the p53 family.
  • Gene expression analysis was performed following DNA damage and overexpression of p53 family members.
  • Functional assays, including apoptosis induction and gene inactivation studies, were conducted to assess EGR2's role.

Main Results:

  • Early growth response 2 (EGR2) was identified as a direct transcriptional target of p53, p63, and p73.
  • EGR2 expression is upregulated by DNA damage-induced p53 activity and by overexpression of p53 family genes.
  • Overexpression of EGR2 enhanced apoptosis with anticancer agents, while EGR2 inactivation attenuated p53-mediated apoptosis.

Conclusions:

  • Early growth response 2 (EGR2) is a direct transcriptional target of the p53 family.
  • EGR2 contributes to the execution of the p53-dependent apoptotic pathway.
  • These findings identify EGR2 as a key mediator in p53-induced cell death, offering potential therapeutic insights.

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