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

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Increased activity of p53 in senescing fibroblasts

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

DOI 10.1073/pnas.92.18.8348PMC PMC41154

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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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Authors: Atadja, P., Wong, H., Garkavtsev, I., Veillette, C., & Riabowol, K.
Affiliations: University of Calgary (CA)
ORCID: Wong, H
Veillette, C
Riabowol, K
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
DOI: 10.1073/pnas.92.18.8348
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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Increased activity of p53 in senescing fibroblasts

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