Cited by 308Telomeres, Telomerase, and SenescenceCancer-related Molecular PathwaysGenetics, Aging, and Longevity in Model Organisms

Increased activity of p53 in senescing fibroblasts

Open access
Atadja, P, Wong, H, Garkavtsev, I, Veillette, C, Riabowol, K·1995·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.92.18.8348

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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
Published
1995-08-29
Volume
92
Issue
18
Pages
8348-8352
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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