Related Experiment Video

Updated: Sep 27, 2026

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

Interferon regulatory factor-1 (IRF-1) is a mediator for interferon-gamma induced attenuation of telomerase activity

Seung-Hoon Lee1, Jung-Whan Kim, Han-Woong Lee

  • 1Molecular Therapy Research Center, College of Medicine, Sungkyunkwan University, Samsung Medical Center Annex 8F, Seoul, Korea.

Oncogene
|January 25, 2003
PubMed

Insights

Interferon-gamma (IFN-gamma) signaling represses cancer-promoting telomerase activity and human telomerase reverse transcriptase (hTERT) transcription. This repression is mediated by IRF-1, a key regulator identified in this study.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Constitutive telomerase activation is crucial for human cancer development.
  • Interferon-gamma (IFN-gamma) signaling triggers tumor growth arrest via diverse regulatory pathways.

Purpose of the Study:

  • To investigate the role of IFN-gamma signaling in regulating telomerase activity and hTERT transcription.
  • To identify the specific mediator of IFN-gamma-induced telomerase repression.

Main Methods:

  • Assessed hTERT promoter activity in wild-type and IRF-1 deficient murine embryonic fibroblasts (MEFs).
  • Utilized ectopic IRF-1 expression and transfection to modulate telomerase activity.
  • Compared telomerase repression in different human cell lines with varying p53 and HPV E6/E7 status.

Main Results:

  • IFN-gamma signaling was found to repress telomerase activity and hTERT transcription.
  • IRF-1 was identified as a mediator, attenuating hTERT promoter activity upon ectopic expression.
  • IRF-1 deficient MEFs exhibited significantly elevated hTERT promoter activity, which was downregulated by IRF-1 transfection.
  • Telomerase repression by IFN-gamma was less pronounced in p53 mutant cells compared to those with intact p53.

Conclusions:

  • IRF-1 acts as a crucial mediator for IFN-gamma-induced attenuation of telomerase activity and hTERT expression.
  • These findings highlight a novel regulatory mechanism involving IRF-1 in cancer biology.
  • The study provides evidence for IRF-1 as a potential therapeutic target in cancers characterized by telomerase activation.

More Related Videos

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...