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The transcription factor CREBZF is a novel positive regulator of p53

Irene López-Mateo1, M Ángeles Villaronga, Susana Llanos

  • 1Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain.

Cell Cycle (Georgetown, Tex.)
|September 18, 2012
PubMed

Insights

The transcription factor CREBZF stabilizes and activates the tumor suppressor p53, enhancing its anti-cancer functions. CREBZF also protects cells from UV damage and chemotherapy, suggesting a role in cancer prevention.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • CREBZF belongs to the ATF/CREB family of transcription factors.
  • The tumor suppressor p53 plays a critical role in cellular response to stress and DNA damage.
  • HEY1 is known to indirectly activate p53.

Purpose of the Study:

  • To investigate the functional interaction between CREBZF and p53.
  • To elucidate the role of CREBZF in p53-mediated cellular responses.

Main Methods:

  • Yeast two-hybrid screening to identify interacting proteins.
  • In vitro interaction assays (co-immunoprecipitation).
  • Western blotting to assess protein levels and modifications.
  • Cell viability assays (UV radiation, 5-fluorouracil treatment).

Main Results:

  • CREBZF directly interacts with both HEY1 and p53.
  • CREBZF expression stabilizes and activates p53, enhancing its transcriptional activity, particularly in synergy with HEY1.
  • Depletion of CREBZF reduces p53 levels and inhibits HEY1-mediated p53 activation.
  • CREBZF induces posttranslational modifications of p53 that prevent its degradation.
  • CREBZF expression protects cells from UV-induced death and increases sensitivity to 5-fluorouracil.

Conclusions:

  • CREBZF is a novel functional interactor of p53.
  • CREBZF enhances p53 tumor suppressor activity through stabilization and posttranslational modification.
  • CREBZF plays a protective role against DNA damage and sensitizes cells to chemotherapy, suggesting its involvement in tumor suppression.

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