The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Telomerase modulates Wnt signalling by association with target gene chromatin
Open accessAbstract
Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.
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“As expected, AAV9-mTERT-DN treatment increased CyclinD1 expression in a number of tissues (Fig 5A and B), in accordance with previous findings (Park et al, 2009).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Park et al, 2009
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“These results are consistent with previous findings that TERT can act as a transcriptional modulator not only in highly proliferating cells but also in terminally differentiated cells.16,27”
From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [27]
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“in agreement with the proposed role of TERT as activator of genes of the Wnt pathway (Park et al, 2009), tissues with increased TERT expression also showed increased expression of active β-catenin, as well as of its target gene cyclinD1, which in turn may mediate some of the known effects of TERT improving stem cell mobilization (Flores et al, 2005; Reya & Clevers, 2005; Sarin et al, 2005).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Park et al, 2009
In the citing paper
“Stable overexpression of TERT in mouse skin enhanced the ability of bulge stem cells to enter cell cycle when stimulated with phorbol esters (147).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [147]
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Citations
Cites
Wnt signalling in stem cells and cancer
Reya, T., & Clevers, H. (2005) · Nature · doi:10.1038/nature03319 · Cited by 3,666
Restoration of p53 function leads to tumour regression in vivo
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Self-citationDepletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4
Kořínek, V., Barker, N., Moerer, P., van Donselaar, E. V., Huls, G., Peters, P., & Clevers, H. (1998) · Nature Genetics · doi:10.1038/1270 · Cited by 1,704
Essential role of mouse telomerase in highly proliferative organs
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Lustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198
De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin
Gat, U., DasGupta, R., Degenstein, L., & Fuchs, E. (1998) · Cell · doi:10.1016/s0092-8674(00)81631-1 · Cited by 1,089
The many ways of Wnt in cancer
Polakis, P. G. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.007 · Cited by 886
Regulation of Telomerase by Telomeric Proteins
Smogorzewska, A., & de Lange, T. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.071403.160049 · Cited by 813
Proteins of the Myc Network: Essential Regulators of Cell Growth and Differentiation
Arsenian‐Henriksson, M., & Lüscher, B. (1996) · Advances in cancer research · doi:10.1016/s0065-230x(08)60353-x · Cited by 781
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Items 701–710 of 710
Telomerase reverse transcriptase as a core regulator of brain health
Shim, H. S., & DePinho, R. A. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.08.003
The Role of Telomerase in Cellular Stress Response—Therapeutic Potential of Telomerase Inhibitors
Pawlak, S., Kostrzewa, M., Lisiak, N., & Rubiś, B. (2026) · Biomedicines · doi:10.3390/biomedicines14102171
hTERT associates with Rab7A to enhance autophagy and rescue oxLDL induced endothelial dysfunction
Machiraju, P., Srinivas, R., Shetty, R., Mukhopadhyay, R., Heymans, S. R. B., & Ghosh, A. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1882233
Telomere Dynamics in Congenital Heart Defects: Hidden Architects of Cardiogenesis?
Joshi, R. O., Nath, S., & Gupta, S. (2026) · Human Mutation · doi:10.1155/humu/5547171
“Yet, this study significantly extends the understanding of the extratelomeric roles of telomerase, positioning TERT as a transcriptional coregulator in developmental and cancer-related pathways [39].”
BindingDB Entry 50043794: Telomere maintenance as a target for drug discovery.
BindingDB (2014) · UC San Diego · doi:10.7270/q2t43vkj
The role of telomerase in brain during ageing and under dietary restriction
Czapiewski, R. (2013)
BIOGENESIS OF TELOMERASE RNA IN FISSION YEAST
Tang, W. (2012)
The role of the cell attachment in the regulation of telomerase during keratinocyte differentiation
Cereser, B. (2010) · OpenGrey (Institut de l'Information Scientifique et Technique)
Metadata
- Authors
- Park, J.-I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., McLaughlin, M., Veenstra, T. D., Nusse, R., McCrea, P. D., & Artandi, S. E.
- Affiliations
- Stanford Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- National Cancer Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Artandi, Steven E.
- ORCID
- Venue
- Nature
- Published
- 2009-07
- Volume
- 460
- Issue
- 7251
- Pages
- 66-72
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4349391
- OpenAlex
- W2086316954
- Cited by
- 707
- References
- 51
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 23 · 2023: 41 · 2022: 32 · 2021: 48 · 2020: 48 · 2019: 34 · 2018: 38 · 2017: 29 · 2016: 43 · 2015: 48 · 2014: 58 · 2013: 58 · 2012: 60
- FWCI
- 21.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (CA111691, R01CA125453, CA125453, R01CA111691, P30CA124435)
- National Institute of General Medical Sciences (R01GM052112)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- telomerase, telomerase reverse transcriptase, Wnt/β-catenin signaling, SMARCA4, chromatin remodeling, transcriptional regulation, epidermal stem cells, stem cell self-renewal, carcinogenesis, anterior-posterior axis, homeotic transformation, promoter, SWI/SNF complex
- MeSH terms
- Animals, Cell Line, Choristoma, Chromatin, DNA Helicases, HeLa Cells, Humans, Intestine, Small, Nuclear Proteins, Oocytes, Plasmids, Promoter Regions, Genetic, Transcription Factors, Xenopus laevis, Signal Transduction, Genes, Reporter, Telomerase, Somites, Wnt Proteins, beta Catenin, Mice, Wnt3 Protein
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