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Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

IRF-5 is a mediator of the death receptor-induced apoptotic signaling pathway

Guodong Hu1, Betsy J Barnes2

  • 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231; New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103.

The Journal of Biological Chemistry
|November 26, 2008
PubMed

Insights

Interferon regulatory factor 5 (IRF-5) promotes tumor cell death by sensitizing them to TRAIL-induced apoptosis. This newly identified mediator enhances cell death signaling, particularly when combined with type I interferons.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Immunology

Background:

  • Cellular stress responses are regulated by genetic networks.
  • Interferon regulatory factor 5 (IRF-5) is involved in innate immunity and DNA damage-induced apoptosis.
  • Tumor suppressor p53 influences cell survival and death balance.

Purpose of the Study:

  • To investigate the role of IRF-5 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR) signaling.
  • To elucidate the mechanism by which IRF-5 mediates apoptosis.

Main Methods:

  • Investigated IRF-5's role in TRAIL-induced apoptosis in tumor cells.
  • Assessed the impact of type I interferons on TRAIL-induced apoptosis in IRF-5 deficient cells.
  • Analyzed IRF-5's involvement in signaling pathways upstream of caspase 8 activation.
  • Examined TRAIL-induced phosphorylation and nuclear localization of IRF-5.

Main Results:

  • IRF-5 sensitizes tumor cells to TRAIL-induced apoptosis and cell death.
  • Type I interferons enhance TRAIL-induced cell death in an IRF-5-dependent manner.
  • Cells lacking IRF-5 show a diminished response to TRAIL and interferons.
  • IRF-5 acts upstream of caspase 8, increasing its activation.
  • TRAIL signaling leads to IRF-5 phosphorylation and nuclear translocation, activating DR signaling components.

Conclusions:

  • IRF-5 is a novel mediator of death receptor signaling.
  • IRF-5 plays a critical role in promoting apoptosis via the TRAIL pathway.
  • This study provides molecular insights into TRAIL-induced IRF-5 signaling in cancer cells.

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