The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT)
Open accessAbstract
Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. The human telomerase catalytic subunit (hTERT) is a rate limiting determinant of the enzymatic activity of human telomerase. In the previous study, we identified the proximal 181 bp core promoter responsible for transcriptional activity of the hTERT gene. To identify the regulatory factors of transcription, transient expression assays were performed using hTERT promoter reporter plasmids. Serial deletion assays of the core promoter revealed that the 5'-region containing the E-box, which binds Myc/Max, as well as the 3'-region containing the GC-box, which binds Sp1, are essential for transactivation. The mutations introduced in the E-box or GC-box significantly decreased transcriptional activity of the promoter. Overexpression of Myc/Max or Sp1 led to significant activation of transcription in a cell type-specific manner, while Mad/Max introduction repressed it. However, the effects of Myc/Max on transactivation were marginal when Sp1 sites were mutated. Western blot analysis using various cell lines revealed a positive correlation between c-Myc and Sp1 expression and transcriptional activity of hTERT. Using fibroblast lineages in different stages of transformation, we found that c-Myc and Sp1 were induced to a dramatic extent when cells overcame replicative senescence and obtained immortal characteristics, in association with telomerase activation. These findings suggest that c-Myc and Sp1 cooperatively function as the major determinants of hTERT expression, and that the switching functions of Myc/Max and Mad/Max might also play roles in telomerase regulation.
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Cites
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Cited by
Human Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898
Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal
Mitchell, T. J., Turajlic, S., Rowan, A., Nicol, D., Farmery, J. H. R., O’Brien, T., Martincorena, I., Tarpey, P., Angelopoulos, N., Yates, L. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.020 · Cited by 513
Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
Kyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347
Self-citationRegulation of the human catalytic subunit of telomerase (hTERT)
Daniel, M., Peek, G. W., & Tollefsbol, T. O. (2012) · Gene · doi:10.1016/j.gene.2012.01.095 · Cited by 266
Xu, D., Wang, Q., Gruber, A., Björkholm, M., Chen, Z., Zaid, A., Selivanova, G., Peterson, C., Wiman, K. G., & Pisa, P. (2000) · Oncogene · doi:10.1038/sj.onc.1203890 · Cited by 257
Metadata
- Authors
- Kyo, S.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-02-01
- Volume
- 28
- Issue
- 3
- Pages
- 669-677
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2039709545
- Cited by
- 494
- References
- 43
- FWCI
- 17.39
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kyo, S. (2000). Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Research. https://doi.org/10.1093/nar/28.3.669
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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