The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer
Open accessAbstract
A mutant promoter's partner in crime: Telomerase is an enzyme that maintains the ends of chromosomes. TERT , the gene coding for the enzyme's catalytic subunit, is not expressed in healthy somatic cells, but its expression is reactivated in the majority of human cancers. The resultant high levels of telomerase help cancer cells survive and multiply. Recurrent mutations in the promoter region of TERT are associated with high telomerase levels in multiple cancer types. Bell et al. show that a specific transcription factor called GABP is selectively recruited to the mutant form of the TERT promoter, which activates TERT gene expression Science , this issue p. 1036
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In glioblastomas, sporadic TERT mutations activate transcription by recruiting GABPA.
“In glioblastomas, sporadic TERT mutations were shown to activate transcription by enabling the recruitment of the transcription factor GA-binding protein α-chain (GABPA)160.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [160]
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Self-citation
- Authors
- Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. D., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., Wiencke, J. K., Wrensch, M. R., Chang, S. M., Walsh, K. M., Myong, S., Song, J. S., & Costello, J. F.
- Affiliations
- University of California, San Francisco (US)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Song, Jun S.
- Costello, Joseph F.
- ORCID
- Venue
- Science
- Published
- 2015-05-29
- Volume
- 348
- Issue
- 6238
- Pages
- 1036-1039
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4456397
- OpenAlex
- W1560916735
- Cited by
- 566
- References
- 44
- Citations by year
- 2026: 29 · 2025: 35 · 2024: 30 · 2023: 51 · 2022: 61 · 2021: 55 · 2020: 59 · 2019: 50 · 2018: 55 · 2017: 45 · 2016: 66 · 2015: 29
- FWCI
- 47.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R01CA163336)
- NCI (P50CA097257, P01CA118816-06, R01CA169316-01, R25CA112355, R01CA52689)
- Sontag Foundation Distinguished Scientist Award
- Grove Foundation
- Karen Osney Brownstein Endowed Chair
- Anne and Jason Farber Foundation
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- TERT promoter mutation, telomerase reverse transcriptase, telomerase reactivation, glioblastoma, replicative senescence, apoptosis evasion, tumor initiation, transcriptional activation
- MeSH terms
- Alleles, Glioblastoma, Humans, Promoter Regions, Genetic, Protein Binding, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Telomerase, Cell Line, Tumor, GA-Binding Protein Transcription Factor, Protein Multimerization
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