Increased activity of p53 in senescing fibroblasts
Open accessAbstract
The p53 tumor-suppressor protein binds DNA and activates the expression of a 21-kDa protein that inhibits both the activity of cyclin-dependent kinases and the function of proliferating cell nuclear antigen. Since p21 expression has been reported to increase 10- to 20-fold as human diploid fibroblasts lose the ability to replicate, we examined the expression and activity of p53 during replicative aging. Similar levels of total p53 mRNA and protein were expressed in low-passage (young) and high-passage (old) cells but both DNA binding activity in vitro and transcriptional activity of p53 in vivo were increased severalfold in high-passage cells. While the basis of increased p53 activity is presently unclear, it is not correlated with differential phosphorylation or changes in p53-mouse double minute 2 gene product interactions. These results provide evidence for the activation of a protein involved in the control of cell cycle checkpoints during cellular aging, in the absence of increased expression.
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- Authors
- Atadja, P., Wong, H., Garkavtsev, I., Veillette, C., & Riabowol, K.
- Affiliations
- University of Calgary (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-08-29
- Volume
- 92
- Issue
- 18
- Pages
- 8348-8352
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC41154
- OpenAlex
- W1996966832
- Cited by
- 308
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 13 · 2013: 9 · 2012: 7
- FWCI
- 9.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council Canada
- Medical Research Council
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- p53, replicative senescence, fibroblasts, p21, tumor suppressor proteins, DNA-binding activity, transcriptional activation, cell cycle checkpoints, cellular aging, cyclin-dependent kinases, proliferating cell nuclear antigen, p53 phosphorylation, MDM2
- MeSH terms
- Adult, Base Sequence, Binding Sites, Cell Line, DNA, Fibroblasts, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Molecular Sequence Data, Nuclear Proteins, Oligodeoxyribonucleotides, Phosphorylation, Proto-Oncogene Proteins, RNA, Messenger, Tumor Suppressor Protein p53, Cellular Senescence, Proto-Oncogene Proteins c-mdm2
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