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EPSIN 3, A Novel p53 Target, Regulates the Apoptotic Pathway and Gastric Carcinogenesis

Jinichi Mori1, Chizu Tanikawa2, Naomi Ohnishi3

  • 1Laboratory of Clinical Genome sequencing, Department of Computational biology and medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, Japan.

Neoplasia (New York, N.Y.)
|February 3, 2017
PubMed
Abstract

Insights

Epsin 3 is a newly identified p53 target gene that plays a crucial role in apoptosis. Its downregulation, observed in gastric cancer and inflammation, confers resistance to cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p53 activation by cellular stress triggers target gene transcription.
  • Investigating p53's complete downstream pathway is essential.
  • EPSIN 3 was identified as a novel p53 target gene.

Purpose of the Study:

  • To confirm EPSIN 3 as a p53 target.
  • To elucidate the role of EPSIN 3 in p53-mediated apoptosis.
  • To analyze EPSIN 3 expression in various conditions and tissues.

Main Methods:

  • Reporter and CHIP assays to validate p53 binding sites in the EPSIN 3 locus.
  • Assessing DNA damage-induced apoptosis in EPSIN 3-knockdown cells and Epsin 3-deficient mice.
  • Evaluating EPSIN 3 expression in gastric cancer, normal gastric mucosa, and gastritis models.

Main Results:

  • p53 directly induced EPSIN 3 expression via promoter and intronic binding elements.
  • EPSIN 3 knockdown conferred resistance to DNA damage-induced apoptosis in vitro and in vivo.
  • EPSIN 3 expression was reduced in gastric cancer and repressed by inflammation (H. pylori, indomethacin).

Conclusions:

  • EPSIN 3 is a novel p53 target and a key mediator of apoptosis.
  • Downregulation of EPSIN 3, due to inflammation or p53 inactivation, leads to apoptosis resistance.
  • Apoptosis resistance is a characteristic feature of cancer cells.

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