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

Published on: August 4, 2019

PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53

Cheol-Hee Yoon1, Eun-Soo Lee, Dae-Seog Lim

  • 1Department of Biological Sciences, Sungkyunkwan University, Choenchoen-Dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, South Korea.

Proceedings of the National Academy of Sciences of the United States of America
|May 7, 2009
PubMed

Insights

The protein kinase R (PKR) is a p53 target gene crucial for tumor suppression. Genotoxic stress activates p53, inducing PKR expression, leading to translational inhibition, apoptosis, and reduced tumor growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Type I interferon-induced expression of double-stranded RNA-activated protein kinase (PKR) is a known antiviral mechanism.
  • The role of PKR in p53-mediated tumor suppression and its expression in the context of p53 remains largely unexplored.

Purpose of the Study:

  • To investigate the relationship between p53 and PKR expression.
  • To elucidate the role of PKR in p53-mediated tumor suppression.

Main Methods:

  • Analysis of PKR promoter activity following p53 activation by genotoxic stress.
  • Investigating the p53/PKR/eukaryotic initiation factor-2alpha (elF2a) pathway.
  • Assessing tumor growth and drug resistance in PKR-knockdown colon cancer cells in vivo.

Main Results:

  • PKR is identified as a p53 target gene, with its expression induced by genotoxic stress via a novel cis-acting element.
  • p53 activation induces translational inhibition and apoptosis through the p53/PKR/elF2a pathway.
  • PKR knockdown in human colon cancer cells resulted in accelerated tumor growth and resistance to anti-cancer drugs in mice.

Conclusions:

  • PKR plays a significant role in the tumor-suppressor function of p53 under genotoxic conditions.
  • p53-mediated tumor suppression is, in part, attributable to the induction of PKR.
  • Targeting the p53-induced PKR pathway may offer therapeutic strategies for cancer treatment.

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