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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

T Kidokoro1, C Tanikawa, Y Furukawa

  • 1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Oncogene
|September 18, 2007
PubMed

Insights

The tumor suppressor p53 protein indirectly inhibits cancer growth by suppressing CDC20. Targeting CDC20 shows potential for broad-spectrum cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The p53 protein is crucial in preventing malignant transformation by regulating genes involved in cell cycle, apoptosis, and senescence.
  • The function of genes suppressed by p53 during carcinogenesis remains largely unknown.
  • Understanding p53-suppressed genes is vital for cancer research.

Purpose of the Study:

  • To investigate the role of p53-suppressed genes in carcinogenesis.
  • To identify specific genes downregulated by p53 and their significance in cancer development.

Main Methods:

  • Analysis of whole-genome expression profiles from cells with introduced wild-type p53 and clinical cancer tissues.
  • Investigated the regulation of CDC20 expression by p53, including its promoter elements (CDE-CHR).
  • Utilized small interference RNA (siRNA) to silence p53 and CDC20 in cellular models.

Main Results:

  • Identified CDC20 as a gene frequently upregulated in malignancies and suppressed by p53 introduction.
  • Demonstrated that genotoxic stresses suppress CDC20 expression in a p53- and p21-dependent manner.
  • Showed that p53 silencing increases CDC20 expression, while CDC20 silencing induces G(2)/M arrest and inhibits cancer cell growth.

Conclusions:

  • p53 inhibits tumor cell growth indirectly through the regulation of CDC20.
  • CDC20 is a potential therapeutic target for various human cancers.
  • Further research into CDC20's role in cancer is warranted.

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