The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
The Wilms' Tumor 1 Tumor Suppressor Gene Represses Transcription of the Human Telomerase Reverse Transcriptase Gene
Open accessAbstract
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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“Several transcriptional repressors, including Wilms' tumor 1 tumor suppressor (WT1) and myeloidspecific zinc finger protein-2 (MZF-2) are also known to repress hTERT transcription via binding to their specific sites on the promoter, although the mechanisms of repression remain unclear.(73,74)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [73]
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Metadata
- 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)
- 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
- 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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