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Updated: Aug 14, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated gene

B Guan1, P Yue, G L Clayman

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Journal of Cellular Physiology
|May 31, 2001
PubMed

Insights

DR4 (TRAIL-R1) expression increases following DNA damage, similar to other TRAIL receptors. This induction is dependent on the wild-type p53 tumor suppressor, indicating DR4 is a p53-regulated gene.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • DR4 (TRAIL-R1) is a cell surface receptor initiating apoptosis upon binding TRAIL.
  • Other TRAIL receptors (DR5, DcR1, DcR2) are induced by DNA damage and regulated by p53.
  • The regulation of DR4 expression by DNA damage and p53 was previously unknown.

Purpose of the Study:

  • To investigate whether DR4 expression is affected by DNA damage and p53.
  • To elucidate the regulatory mechanisms controlling DR4 gene expression in response to cellular stress.

Main Methods:

  • DNA damage induction using ionizing radiation and chemotherapeutic agents.
  • Analysis of DR4 expression in cells with varying p53 status (wild-type, mutant, E6-treated, p53-overexpressing).
  • Assessment of transcriptional regulation using actinomycin D.

Main Results:

  • DR4 expression is enhanced by DNA-damaging agents, mirroring DR5 and Fas regulation.
  • DR4 induction is predominantly observed in cells with wild-type p53.
  • HPV 16 E6 gene transfection suppressed DR4 induction, while exogenous p53 upregulated DR4.
  • Actinomycin D abolished DNA-damaging agent-induced DR4 expression, confirming transcriptional control.

Conclusions:

  • DR4 is a DNA damage-inducible gene.
  • DR4 expression is regulated by the wild-type p53 tumor suppressor.
  • DR4 represents a novel p53-regulated target gene involved in cellular response to DNA damage.

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