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Related Experiment Videos

p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression.

Hidetaka Uramoto1, Hiroto Izumi, Tomoko Ise

  • 1Department of Molecular Biology, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

The Journal of Biological Chemistry
|June 25, 2002
PubMed
Summary

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The protein Y-box binding protein 1 (YB-1) is upregulated by cisplatin, a chemotherapy drug. The transcription factors p73 and c-Myc are essential for this YB-1 gene activation, with p73 enhancing c-Myc binding to DNA.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Y-box binding protein 1 (YB-1) is a DNA-responsive protein involved in cell proliferation.
  • YB-1 recognizes DNA damaged by cisplatin, a common chemotherapy agent.
  • YB-1 expression is induced by DNA damage.

Purpose of the Study:

  • To investigate the molecular mechanisms regulating YB-1 gene expression in response to cisplatin.
  • To determine the roles of transcription factors c-Myc and p73 in YB-1 promoter activity.
  • To elucidate the interaction between p73 and c-Myc in regulating YB-1 transcription.

Main Methods:

  • Quantitative analysis of YB-1 mRNA levels following cisplatin treatment in KB cancer cells.
  • Cotransfection experiments using YB-1 promoter constructs in Saos-2 and HO15.19 cell lines.

Related Experiment Videos

  • In vitro and in vivo interaction studies between p73 and c-Myc using deletion mutants.
  • Assessment of c-Myc-Max complex binding to DNA.

    • Main Results:

    • Cisplatin exposure induced a six-fold increase in YB-1 mRNA levels.
    • Both c-Myc and p73 were found to be critical for YB-1 promoter transactivation.
    • An intact E-box element in the YB-1 promoter was necessary for cisplatin response.
    • p73 and c-Myc interact physically, and p73 enhances c-Myc-Max complex recruitment to the YB-1 promoter's E-box.

    Conclusions:

    • p73 and c-Myc play a crucial role in the transcriptional regulation of the YB-1 gene.
    • The interaction between p73 and c-Myc, mediated by specific protein domains, is essential for YB-1 induction.
    • p73 facilitates the binding of the c-Myc-Max complex to the YB-1 promoter, thereby promoting transcription in response to cisplatin.