The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16 INK4a
Abstract
Increased mitogenic signaling by positive effectors such as Ras or Myc can trigger senescence in normal cells, a response believed to function as a tumor-suppressive mechanism. We report here the existence of a checkpoint that monitors hypoproliferative signaling imbalances. Normal human fibroblasts with one copy of the c-myc gene inactivated by targeted homologous recombination switched with an increased frequency to a telomere-independent senescent state mediated by the cyclin-dependent kinase inhibitor p16 INK4a . p16 INK4a expression was regulated by the Polycomb group repressor Bmi-1, which we show is a direct transcriptional target of c-Myc. The Myc–Bmi circuit provides a mechanism for the conversion of environmental inputs that converge on c-Myc into discrete cell-fate decisions coupled to cell-cycle recruitment. A mechanism for limiting the proliferation of damaged or otherwise physiologically compromised cells would be expected to have important consequences on the generation of replicatively senescent cells during organismal aging.
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Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
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Ink4a/Arf expression is a biomarker of aging
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Cited by
Dang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390
Aging, Cellular Senescence, and Cancer
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Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
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IRF4 addiction in multiple myeloma
Shaffer, A. L., Emre, N. C. T., Lamy, L., Ngo, V. N., Wright, G., Xiao, W., Powell, J., Dave, S., Yu, X., Zhao, H., et al. (2008) · Nature · doi:10.1038/nature07064 · Cited by 730
Zhang, X.-Y., Varthi, M., Sykes, S. M., Phillips, C., Warzecha, C., Zhu, W., Wyce, A., Thorne, A. W., Berger, S. L., & McMahon, S. B. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.015 · Cited by 427
Metadata
- Authors
- Guney, I., Wu, S., & Sedivy, J. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-02-28
- Volume
- 103
- Issue
- 10
- Pages
- 3645-3650
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2001698191
- Cited by
- 180
- References
- 12
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- closed
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- Guney, I., Wu, S., & Sedivy, J. M. (2006). Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16 INK4a. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0600069103
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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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