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The novel p53 target gene IRF2BP2 participates in cell survival during the p53 stress response

Max Koeppel1, Simon J van Heeringen, Leonie Smeenk

  • 1Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.

Nucleic Acids Research
|December 2, 2008
PubMed

Insights

The tumor suppressor p53 regulates cellular fate. We identified IRF2BP2 as a new p53 target gene that influences cell survival and apoptosis by modulating p53

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The tumor suppressor p53 is crucial for cellular fate determination following genotoxic stress.
  • p53 regulates target genes to promote cell survival via repair or induce apoptosis.
  • The precise mechanisms dictating p53-mediated cellular outcomes remain incompletely understood.

Purpose of the Study:

  • To identify novel p53 target genes that influence cellular decisions after genotoxic insults.
  • To elucidate the role of interferon regulatory factor-2-binding protein-2 (IRF2BP2) in p53-mediated cellular responses.
  • To investigate how IRF2BP2 affects apoptosis and cell survival pathways regulated by p53.

Main Methods:

  • Analysis of IRF2BP2 expression in response to genotoxic agents (actinomycin D, doxorubicin) in cell lines with functional or non-functional p53.
  • Investigation of the interaction between IRF2BP2 and IRF2.
  • Assessment of IRF2BP2's impact on p53-mediated transactivation of p21 and Bax.
  • Functional studies involving IRF2BP2 overexpression and knockdown to evaluate effects on cellular stress response and apoptosis.

Main Results:

  • IRF2BP2 is identified as a direct p53 target gene, upregulated in a p53-dependent manner after actinomycin D treatment.
  • IRF2BP2 expression correlates with the downregulation of IRF2, a known growth-promoting factor.
  • Overexpression of IRF2BP2 impedes p53-mediated transactivation of p21 and Bax, reduces apoptosis induction after doxorubicin treatment, and impacts cellular stress response.
  • Knockdown of IRF2BP2 enhances p21 upregulation and accelerates apoptosis induction following doxorubicin and actinomycin D treatment.

Conclusions:

  • IRF2BP2 is a novel p53 target gene that plays a significant role in modulating p53-dependent cellular fate decisions.
  • IRF2BP2 acts as a negative regulator of p53-mediated apoptosis and influences the expression of key apoptosis-related genes like p21 and Bax.
  • IRF2BP2's function in regulating cellular stress responses and apoptosis provides new insights into the complex mechanisms governing cell survival and death pathways.

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