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Runt-related transcription factor 1 (RUNX1) stimulates tumor suppressor p53 protein in response to DNA damage through

Dan Wu1, Toshinori Ozaki, Yukari Yoshihara

  • 1Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, 666-2 Nitona, Chiba 260-8717, Japan.

The Journal of Biological Chemistry
|November 14, 2012
PubMed

Insights

Runt-related transcription factor 1 (RUNX1) is crucial for the tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • The tumor suppressor p53 is a key regulator of DNA damage response.
  • The role of Runt-related transcription factor 1 (RUNX1) in DNA damage response is not well understood.

Purpose of the Study:

  • To investigate the novel role of RUNX1 in p53-dependent DNA damage response.
  • To elucidate the molecular mechanisms by which RUNX1 influences p53 activity.

Main Methods:

  • Adriamycin (ADR) exposure in p53-proficient cells (HCT116, U2OS).
  • Western blotting to detect p53 and RUNX1 induction.
  • Chromatin immunoprecipitation (ChIP) assays to assess promoter recruitment.
  • RUNX1 knockdown experiments using siRNA.
  • Co-immunoprecipitation to study protein complex formation.

Main Results:

  • RUNX1, like p53, is induced upon ADR exposure and localizes to the nucleus.
  • RUNX1 forms a complex with p53 and is recruited to p53 target gene promoters.
  • RUNX1 enhances p53 transcriptional activity, p53 target gene induction, and ADR-dependent apoptosis.
  • RUNX1 facilitates p53 acetylation at Lys-373/382 by associating with p300 histone acetyltransferase.

Conclusions:

  • RUNX1 is a novel co-factor required for p53 activation in response to DNA damage.
  • RUNX1 promotes p53-mediated transactivation and apoptosis through physical and functional interaction with p53 and p300.
  • This study provides new insights into the molecular mechanisms of p53-dependent DNA damage response.

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