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Different telomere damage signaling pathways in human and mouse cells
Open accessAbstract
Programmed telomere shortening in human somatic cells is thought to act as a tumor suppressor pathway, limiting the replicative potential of developing tumor cells. Critically short human telomeres induce senescence either by activating p53 or by inducing the p16/RB pathway, and suppression of both pathways is required to suppress senescence of aged human cells. Here we report that removal of TRF2 from human telomeres and the ensuing de-protection of chromosome ends induced immediate premature senescence. Although the telomeric tracts remained intact, the TRF2(DeltaBDeltaM)-induced premature senescence was indistinguishable from replicative senescence and could be mediated by either the p53 or the p16/RB pathway. Telomere de-protection also induced a growth arrest and senescent morphology in mouse cells. However, in this setting the loss of p53 function was sufficient to completely abrogate the arrest, indicating that the p16/RB response to telomere dysfunction is not active in mouse cells. These findings reveal a fundamental difference in telomere damage signaling in human and mouse cells that bears on the use of mouse models for the telomere tumor suppressor pathway.
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“Consistent with previous reports (27), G4 mTerc -/ -Ink4a / Arf -/ -MEFs showed an intermediate phenotype of decreased growth rates after 10 population doublings with steady slow proliferation thereafter, indicating that telomere dysfunction suppresses the growth rate, but not the immortalization potential, of Ink4a / Arf -/ -MEFs.”
From Ink4a / Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [27]
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“In MEFs, p19 Arf and p16 Ink4a contribute to the growth arrest incurred by telomere deprotection (14, 27).”
From Ink4a / Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [27]
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“For example, mouse cells are thought to rely primarily on the p53 pathway for both replicative and telomere-dependent senescence (Harvey et al., 1993; Smogorzewska and de Lange, 2002).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Smogorzewska and de Lange, 2002
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“Consistent with the latter, p19 Arf deficiency has been reported to provide partial rescue of growth arrest after acute deprotection of telomeres by expression of a dominant-negative mutant of the telomere binding protein, Trf2, in mouse embryonic fibroblasts (MEFs) (27).”
From Ink4a / Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [27]
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“By contrast, p53 inactivation alone is sufficient to avoid telomere-induced senescence and apoptosis in mice49,50.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [50]
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“Damaged telomeres eventually register as a form of DNA damage (8) triggering among other things a p53-mediated cell cycle arrest (9).”
From Glycolytic Enzymes Can Modulate Cellular Life Span (2005) · cites this paper as [9]
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Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794
Mammalian Telomeres End in a Large Duplex Loop
Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., & de Lange, T. (1999) · Cell · doi:10.1016/s0092-8674(00)80760-6 · Cited by 2,447
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1×
“& & ' 0- " < 8 3* .”
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051
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Cancer, Senescence, and Aging: Translation from Basic Research to Clinics
LLeonart, M. E., Carnero, A., Paciucci, R., Wang, Z., & Shomron, N. (2011) · Journal of Aging Research · doi:10.4061/2011/692301 · Cited by 1
“For example, miR-17-5p is overexpressed in pancreatic cancer [64], squamous cell carcinoma [65], breast cancer [66], hepatocellular cancer [67], renal cell carcinoma [68], and thyroid cancer [69], suggesting a potential oncogenic role of miR-17-5p.”
BackgroundStress factor – dependent differences in molecular mechanisms of premature cell senescence
Petrova, N. V., Velichko, A. K., Petrova, N. V., Razin, S. V., & Kantidze, O. L. (2015) · Biopolymers and Cell · doi:10.7124/bc.0008f4 · Cited by 1
“Furthermore, it was shown that the mean 3’-overhang length of individual chromosomes, rather than the total telomere length [72, 73], and specific proteins present in telomeric regions [74] are important for triggering cell senescence.”
BackgroundTelomere-Binding Proteins in Humans
Dimitrova, N. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-879-9_2 · Cited by 1
“In addition to activating the canonical ATM pathway (80), as described above, exogenous introduction of TRF2DBDM results in p53-dependent cell cycle arrest or apoptosis, depending on the cell type (81, 82 ).”
BackgroundTelomere Biology and Biochemistry
Gardano, L., & Harrington, L. A. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_1 · Cited by 1
Role of telomere binding protein TRF2 in neural differentiation of human embryonic stem cells
Ovando-Roche, P. (2013) · doi:10.25560/24848 · Cited by 1
Mouse Model: Telomeres and Telomerase in Stem Cell and Cancer
Huang, X., & Ju, Z. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-879-9_6 · Cited by 1
“Further experimental evidence suggests that p16 can activate p53-independent checkpoints in response to an artificial telomere dysfunction, which induced by deletion of Trf2 ‐a telomere-binding protein that is necessary for telomere capping function ( 91 ).”
BackgroundOverview of DNA Repair Pathways
Croteau, D. L., & Bohr, V. A. (2013) · CRC Press eBooks · doi:10.1201/b14587-2 · Cited by 1
Toouli, C. D., & Reddel, R. R. (2003) · Springer eBooks · doi:10.1007/978-94-017-0669-8_10 · Cited by 1
Cellular Senescence Pathways in Mouse and Human
Wadhwa, R., Hasan, M. K., & Kaul, S. C. (2003) · Springer eBooks · doi:10.1007/978-94-017-0669-8_12 · Cited by 1
Hahn, W. C. (2003) · Cancer Research and Treatment · doi:10.4143/crt.2003.35.6.467 · Cited by 1
The role of telomere damage in cardiomyocyte ageing
Anderson, R. K. (2016) · Cited by 1
Antiaging and Skin Lightening Microbial Products
Gupta, P. L., Trivedi, U., Rajput, M., Oza, T., Chauhan, J., & Sanghvi, G. V. (2021) · Wiley eBooks · doi:10.1002/9781119717317.ch4 · Cited by 1
Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lungPreprint
Lipskaia, L., Breau, M., Cayrou, C., Churikov, D., Braud, L., Fouillade, C., Curras-Alonso, S., Bauwens, S., Jourquin, F., FIORE, F., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.27.514005 · Cited by 1
Replicative Senescence as an Intrinsic Tumor-Suppressor Mechanism
Chang, S. S. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_8
Signaling Networks Controlling Cellular Senescence
Desai, L. P., Sanders, Y. Y., & Thannickal, V. J. (2014) · Wiley eBooks · doi:10.1002/9781118396292.ch6
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Wolyniec, K. (2008) · Enlighten: Theses (The University of Glasgow) · doi:10.5525/gla.thesis.578
Genomic Instability and DNA Repair
Gagos, S. (2007) · Wiley eBooks · doi:10.1002/9780470025079.chap07.pub2
Palma, M. (2010) · Figshare
Smith, R. (2013) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
In Search for Biomarkers of Aging : A Proteomics Approach
Klooster, R. (2006) · Utrecht University Repository (Utrecht University)
Development of adenoviral vectors for monitoring telomerase activity in living cells
Edqvist, A. (2007) · Lund University Publications (Lund University)
Hultdin, M. (2003) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Martín, E. G. (2011) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Variables Involved in Measuring Cancer Response to Treatment
Kostakoğlu, L. (2008) · PET Clinics · doi:10.1016/j.cpet.2008.08.002
Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses
Bourdeau, V., & Ferbeyre, G. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_3
Shelterin complex in telomere protection: recent insights and pathological significance
Loayza, D., & Kalan, S. (2014) · Cell Health and Cytoskeleton · doi:10.2147/chc.s49687
“41,42 It has since been discovered that telomeres can elicit many DNA repair activities, which are inhibited by shelterin.”
TRANSCRIPTOME STUDIES OF CELL-FATE AND AGING
Larsson, O. S. (2005) · Figshare
Identifying cancer-causing noncoding RNAs
le Sage, & Karel, C. (2008) · Leiden Repository (Leiden University)
Telomeres, Telomerase, and DNA Damage Response in Cancer Therapy
Tamakawa, R., Fleisig, H. B., & Wong, J. M. Y. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4741-2_11
Bischof, O., Dejean, A., & Pineau, P. (2009)
Aging of the Vasculature and Related Systems
Marı́n-Garcı́a, J., Goldenthal, M. J., & Moe, G. W. P. L. (2007) · Springer eBooks · doi:10.1007/978-0-387-74072-0_5
The effect of radiation on cellular ageing
Sabin, R. J. (2012) · Brunel University Research Archive (BURA) (Brunel University London)
Costa, J. (2015) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Induction of p53 Dependent Cellular Senescence Through HdmX Inhibition or YPEL3 Expression
Miller, K. L. (2010) · Journal of Bioresource Management
Donigian, J. R. (2008) · Digital Commons - RU (Rockefeller University) · doi:10.48496/z32n-yn07
Exploring biological risk factors of chronic obstructive pulmonary disease : old age and female sex
Mui, T. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0070956
Regulation of the retinoblastoma tumor suppressor by the novel Ras effector NORE1A.
Barnoud, T. (2015) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/2320
“induction of senescence in a variety of human cell lines (159,164,253,278,279), and furthermore, cross-talk between the p53 and Rb pathways could allow for additional protection against oncogenic Ras bypassing senescence and promote tumorigenesis (250).”
BackgroundTelomeres and the End Replication Problem
Bryan, T. M. (2009) · Royal Society of Chemistry eBooks · doi:10.1039/9781847559852-00217
her2 hyper-activation through the production of carboxy-terminal fragments
Angelini, P. D. (2014) · TDX (Tesis Doctorals en Xarxa)
Biochemical Characterization of hTRF1 and hTEP1, Two Proteins Involved in Telomere Maintenance
Tahmaseb, K. (2007) · OhioLink ETD Center (Ohio Library and Information Network)
Comparative Biology of Glioma Stem Cells and Embryonic Neural Stem Cells in Dogs.
Woolard, K. (2010) · NCSU Libraries Repository (North Carolina State University Libraries)
Stress and cellular aging Associations between stress-related factors and leukocyte telomere length
Savolainen, K. (2016) · Työväentutkimus Vuosikirja
Jolliffe, A. K. (2012) · TSpace (University of Toronto)
Structural dynamics of telomeric overhang accessibility
Hwang, H. (2014) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Vascular Aging: from Smooth Muscle Cell Differentiation to Polyploidization
Zhan, S. (2016) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/28633
Cancer Cell Immortality: Targeting Telomerase
Mender, İ., Dikmen, Z. G., Wright, W. E., & Shay, J. W. (2017) · Wiley eBooks · doi:10.1002/9781119000822.hfcm014
New Insights into the Regulation of Hematopoietic Stem Cell Self-Renewal.
Jones, M. (2015) · Deep Blue (University of Michigan)
Mahemuti, L. (2017) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2017-12222
Overview of the DNA Damage Checkpoint
Dupré, A., & Gautier, J. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-221-2_11
A new species of Phomopsis on Tamarindus indica L.
Arya, A., Arya, C., Agarwal, R. A., & Lal, B. (1999) · National Academy Science Letters
Westin, E. R., Klingelhutz, A. J., Wallrath, L. L., McCray, P. B., Davidson, B. L., & Knudson, C. M. (2010) · doi:10.17077/etd.2xq96sz4
Anti-Aging Medicine LiteratureWatch
(2002) · Rejuvenation Research · doi:10.1089/109454502763485511
Tainer, J. A., & Roy, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734203077.793554727
Laurent, G. (2003) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1005304.195171
Jackson, S. P. (2007) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1059114.511094
Faculty Opinions recommendation of Telomeres in cancer: tumour suppression and genome instability.
Savage, S. A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727224887.793545187
Almouzni, G. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734203077.793553213
Tanaka, T. U., & Eykelenboom, J. K. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734203077.793556803
Cancer Cell Immortality: Targeting Telomerase and Telomeres
Mender, İ., Dikmen, Z. G., & Shay, J. W. (2022) · Wiley eBooks · doi:10.1002/9781119000822.hfcm014.pub2
Noureen, N., & Kang, M. H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.21.655338
“Nevertheless, different levels of telomerase can trigger different signaling cascades which have a substantial impact on cellular processes like proliferation, senescence and apoptosis 44-46 .”
Le rôle de l'oncoprotéine INT6 dans la maintenance des télomères
Benyelles, M. (2015) · theses.fr (ABES) · doi:10.70675/895a5201z1656z4103zbf00zdf282ab374f9
Telomere length in cardiovascular disease and type 2 diabetes
Salpea, K. D. (2011) · UCL Discovery (University College London)
Cudejko, C. (2010) · theses.fr (ABES) · doi:10.70675/3be56540zf3b1z4ee1z99ffz2dbbe7a0dc17
p16INK4a, régulation du cycle cellulaire et microARN
Chien, W. W. (2009) · theses.fr (ABES) · doi:10.70675/dbb5386dzc679z454fzad91z9d53a61231ff
Benkdane, M. (2012) · theses.fr (ABES) · doi:10.70675/45d1370fz6819z4b07zb446zd155483ab1de
3-D Genome organization of DNA damage repair
Banerjee, U. K. (2017) · theses.fr (ABES) · doi:10.70675/25480b49zc194z4a4bzb6b0z2f84dab6ccef
L’échappement à la sénescence induite par chimiothérapie : Un nouveau rôle de la protéine AGR2
Maarouf, A. (2021) · theses.fr (ABES) · doi:10.70675/2804fda4z0d12z4a01za7eezd95a7d0b70d2
Marión, R. M., González, J. C., Flores, J. M., Piñeiro-Yáñez, E., Serrano, R., & Blasco, M. A. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117786
Hartmann, N. R. (2005) · MPG.PuRe (Max Planck Society)
A Critical Review of Telomerase Biology and Model Systems for the Study of Telomerase
Aisenberg, J. C. (2006) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/dpa7-yb56
The Senescent Cell Induced Bystander Effect
Wordsworth, J. (2014)
Telomere, Regulation and Tumorigenesis
Kheirollahi, M. (2012) · Springer eBooks · doi:10.1007/978-94-007-4632-9_4
(2003) · PubMed · Cited by 146
Metadata
- Authors
- Smogorzewska, A., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- ORCID
- Smogorzewska, Agata
- Venue
- The EMBO Journal
- Published
- 2002-08-15
- Volume
- 21
- Issue
- 16
- Pages
- 4338-4348
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC126171
- OpenAlex
- W2126815966
- Cited by
- 482
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 9 · 2022: 3 · 2021: 16 · 2020: 10 · 2019: 9 · 2018: 17 · 2017: 13 · 2016: 14 · 2015: 19 · 2014: 14 · 2013: 20 · 2012: 25
- FWCI
- 28.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health
- National Institute on Aging (AG 16643)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- premature senescence, TRF2, p53, p16/Rb pathway, replicative senescence, tumor suppressor pathways, human-mouse differences, growth arrest, telomere dysfunction
- MeSH terms
- Animals, Cell Line, Chromosome Aberrations, DNA Damage, DNA-Binding Proteins, Fibroblasts, Humans, Signal Transduction, Tumor Suppressor Protein p53, Telomere, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Telomeric Repeat Binding Protein 2, Mice
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