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Repression of c- fos Transcription and an Altered Genetic Program in Senescent Human Fibroblasts
Abstract
Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H- ras , c- myc , and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c- fos proto-oncogene. The loss of c- fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c- fos ; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.
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Cited by
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
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
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Self-citationKrtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
Self-citationOxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116
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Metadata
- Authors
- Seshadri, T., & Campisi, J.
- Venue
- Science
- Published
- 1990-01-12
- Volume
- 247
- Issue
- 4939
- Pages
- 205-209
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2085797277
- Cited by
- 481
- References
- 0
- FWCI
- 31.95
- Type
- journal article
- Language
- en
- Open access
- closed
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- Seshadri, T., & Campisi, J. (1990). Repression of c- fos Transcription and an Altered Genetic Program in Senescent Human Fibroblasts. Science. https://doi.org/10.1126/science.2104680
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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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