Identification of Mad as a repressor of the human telomerase (hTERT) gene

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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Published on: April 13, 2015

S Oh1, Y H Song, J Yim

  • 1National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.

Oncogene
|March 21, 2000
PubMed

Insights

The transcription factor Mad represses the human telomerase reverse transcriptase (hTERT) gene in mortal cells. Cancer cells activate telomerase by reducing Mad or increasing Myc, a repressor of Mad.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Telomere maintenance is crucial for cellular immortality and cancer development.
  • Telomerase activation, mediated by the hTERT gene, is a hallmark of many human cancers.
  • The mechanisms repressing hTERT in normal mortal cells remain largely unknown.

Purpose of the Study:

  • To identify genes responsible for repressing human telomerase reverse transcriptase (hTERT) expression in mortal cells.
  • To elucidate the regulatory mechanisms governing hTERT gene expression in cancer development.

Main Methods:

  • Expression cloning approach to screen for repressor genes.
  • Genetic screening to identify factors regulating hTERT promoter activity.
  • Mutation analysis of DNA binding sites and protein expression level comparisons.

Main Results:

  • The transcription factor Mad was identified as a repressor of the hTERT gene.
  • Mutations in Mad binding sites led to significant de-repression of hTERT promoter activity in mortal cells.
  • Ectopic expression of Myc counteracted Mad-mediated repression, and Myc/Mad protein levels differed between mortal and immortal cells.

Conclusions:

  • Mad acts as a direct negative regulator of hTERT in mortal cells.
  • The repression of hTERT by Mad can be overcome by Myc induction, potentially contributing to cellular immortalization in cancer.

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