Cited by 148Telomeres, Telomerase, and SenescenceGenomics and Chromatin DynamicsCancer-related molecular mechanisms research

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The Wilms' Tumor 1 Tumor Suppressor Gene Represses Transcription of the Human Telomerase Reverse Transcriptase Gene

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Oh, Sangtaek, Song, Younghwa, Yim, Jeongbin, Kim, Tae Kook·1999·Journal of Biological Chemistry

DOI 10.1074/jbc.274.52.37473

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Abstract

Regulation of the human telomerase reverse transcriptase (hTERT) gene is the primary determinant for telomerase enzyme activity, which is found in tumor cells but is largely absent from normal somatic cells. Recent studies have shown that Myc protein can transcriptionally activate the hTERT gene. However, little is known about the repression mechanism of the hTERT gene and telomerase enzyme. Here, we developed an expression cloning strategy to identify cDNAs whose products can repress hTERT promoter activity in telomerase-positive immortal cells. Using this screen, we isolated the Wilms' tumor 1 suppressor gene (WT1). WT1 can repress hTERT promoter activity in 293 kidney cells. The WT1 binding site on the hTERT promoter was identified by deletional analysis. Alteration of the WT1 binding site markedly derepresses transcription from an isolated hTERT promoter by inhibiting interaction of WT1 with DNA. These specific repression effects of WT1 were not observed in HeLa cells, which express no endogenous WT1. Furthermore, we show that WT1 can repress the endogenous hTERT promoter and telomerase enzyme activities. These results suggest that WT1 may be a transcriptional repressor of the hTERT gene, at least in some specific cells.

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Authors: Oh, S., Song, Y., Yim, J., & Kim, T. K.
Affiliations: Seoul National University (KR)
Harvard University (US)
Corresponding author: Kim, Tae Kook
ORCID: Oh, Sangtaek
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1999-12
Volume: 274
Issue: 52
Pages: 37473-37478
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.274.52.37473
OpenAlex: W2046268297
Cited by: 148
References: 35
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 3
FWCI: 6.34
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7617 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: Wilms tumor 1, WT1, telomerase reverse transcriptase, hTERT, transcriptional repression, telomerase, promoter regulation, transcriptional repressor, c-Myc, expression cloning, kidney cells
MeSH terms: DNA-Binding Proteins, HeLa Cells, Humans, Promoter Regions, Genetic, Repressor Proteins, RNA, Transcription Factors, Transcription, Genetic, Genes, Tumor Suppressor, Telomerase, WT1 Proteins

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The Wilms' Tumor 1 Tumor Suppressor Gene Represses Transcription of the Human Telomerase Reverse Transcriptase Gene

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