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

Oncogene volume 19, pages 1485–1490 (2000)Cite this article

Abstract

Activation of telomerase, which has been frequently associated with cellular immortality, may constitute a key step in the development of human cancer. De-repression in the expression of its catalytic subunit hTERT gene has been proposed to directly link to the telomerase activation in tumor cells. Little is known about the mechanism how the hTERT gene is repressed in telomerase-negative mortal cells. This study was conducted, using an expression cloning approach, with the aim of identifying the gene(s) responsible for repressing the hTERT gene expression. Using this genetic screen, we isolated the transcription factor Mad as a repressor. Mutation of its DNA binding sites caused significant de-repression of hTERT promoter activity in mortal cells. This Mad-mediated repression of the hTERT promoter in mortal cells was counteracted by ectopic expression of Myc. The antagonism between Mad and Myc was also observed with an endogenous hTERT promoter. Their potential roles in differential hTERT promoter activities were further supported by the relative amounts of Mad and Myc proteins detected in immortal and mortal cells. Thus, Mad may be a direct negative regulator of hTERT in mortal cells and this repression mechanism can be inhibited by induction of Myc in immortal cells.

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Acknowledgements

This work was supported by the Creative Research Initiatives of the Korean Ministry of Science and Technology, Republic of Korea.

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Authors and Affiliations

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

    Sangtaek Oh, Young-Hwa Song, Jeongbin Yim & Tae Kook Kim

  2. Department of Biological Chemistry and Molecular Pharmacology, Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Tae Kook Kim

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  1. Sangtaek Oh
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Oh, S., Song, YH., Yim, J. et al. Identification of Mad as a repressor of the human telomerase (hTERT) gene. Oncogene 19, 1485–1490 (2000). https://doi.org/10.1038/sj.onc.1203439

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