The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Werner syndrome protein limits MYC-induced cellular senescence
Open accessAbstract
The MYC oncoprotein is a transcription factor that coordinates cell growth and division. MYC overexpression exacerbates genomic instability and sensitizes cells to apoptotic stimuli. Here we demonstrate that MYC directly stimulates transcription of the human Werner syndrome gene, WRN , which encodes a conserved RecQ helicase. Loss-of-function mutations in WRN lead to genomic instability, an elevated cancer risk, and premature cellular senescence. The overexpression of MYC in WRN syndrome fibroblasts or after WRN depletion from control fibroblasts led to rapid cellular senescence that could not be suppressed by hTERT expression. We propose that WRN up-regulation by MYC may promote MYC-driven tumorigenesis by preventing cellular senescence.
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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
Alcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13742 · Cited by 1,008 · cited 1×
“1997), as well as p16 (Alcorta et al. 1996), the major inhibitor of Rb phosphorylation, in WRN and control cells (Fig.”
BackgroundDirect activation of TERT transcription by c-MYC
Wu, K.-J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., & Dalla-Favera, R. (1999) · Nature Genetics · doi:10.1038/6010 · Cited by 893
Self-citationBypass of Senescence After Disruption of p21 CIP1/WAF1 Gene in Normal Diploid Human Fibroblasts
Brown, J. P., Wei, W., & Sedivy, J. M. (1997) · Science · doi:10.1126/science.277.5327.831 · Cited by 804
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts
Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. A., & Kipling, D. (2000) · Nature Genetics · doi:10.1038/71630 · Cited by 332
Cited by
Living on a break: cellular senescence as a DNA-damage response
d'Adda di Fagagna, F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2440 · Cited by 1,170
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
Gil, J., & Peters, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1987 · Cited by 843
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Schaub, F. X., Dhankani, V., Berger, A. C., Trivedi, M., Richardson, A. B., Shaw, R., Zhao, W., Zhang, X., Ventura, A., Liu, Y., et al. (2018) · Cell Systems · doi:10.1016/j.cels.2018.03.003 · Cited by 431
“…pathways, as previously observed in experimental systems upon manipulation of MYC levels (Dominguez-Sola et al., 2007; Gomez-Roman et al., 2006; Grandori et al., 2003, 2005; Grewal et al., 2005; Hnisz et al., 2013; Johnston et al., 1999; Moser et al., 2012; Robinson et al., 2009; for a review…”
Self-citationGewin, L., Myers, H., Kiyono, T., & Galloway, D. A. (2004) · Genes & Development · doi:10.1101/gad.1214704 · Cited by 277
Oncogene-induced senescence: the bright and dark side of the response
Gorgoulis, V. G., & Halazonetis, T. D. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.07.013 · Cited by 257
Metadata
- Authors
- Grandori, C., Wu, K.-J., Fernandez, P., Ngouenet, C., Grim, J., Clurman, B. E., Moser, M. J., Oshima, J., Russell, D. W., Swisshelm, K., Frank, S., Amati, B., Dalla-Favera, R., & Monnat, R. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-07-01
- Volume
- 17
- Issue
- 13
- Pages
- 1569-1574
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2135963451
- Cited by
- 180
- References
- 5
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: Werner syndrome protein limits MYC-induced cellular senescence. https://app.cochat.ai/papers/10.1101/gad.1100303
- The paper
- Grandori, C., Wu, K.-J., Fernandez, P., Ngouenet, C., Grim, J., Clurman, B. E., Moser, M. J., Oshima, J., Russell, D. W., Swisshelm, K., Frank, S., Amati, B., Dalla-Favera, R., & Monnat, R. J. (2003). Werner syndrome protein limits MYC-induced cellular senescence. Genes & Development. https://doi.org/10.1101/gad.1100303
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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