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Increased p53 Protein Associated with Aging in Human Diploid Fibroblasts
Abstract
Molecular changes associated with cellular aging in a strain of human diploid fibroblasts, IMR-90, were addressed by analyzing the expression of the tumor suppressor protein, p53. In all studies, IMR-90 cultures were characterized as "young" or "near-senescent" based on morphology, rate of population doubling, capacity for DNA synthesis, and presence of established markers for senescence. When p53 was immunoprecipitated by monoclonal antibodies and detected by Western immunoblot analysis, more protein per cell was detected in the near-senescent cultures. A greater than 10-fold increase in p53 protein was measured with the PAb 1801 (N-terminal-specific) anti-p53 antibody, whereas PAb 122 (C-terminal-specific) measured a 5-fold increase. Although near-senescent cultures demonstrated a higher level of p53 than young cells, these cultures had similar charges and molecular weight p53 isoforms when analyzed by two-dimensional Western blots. When p53 RNA was compared to total RNA there was a decrease in p53 RNA with age, but on a per cell basis p53 RNA was elevated. These results provide evidence for transcriptional regulation of p53 during aging and support the hypothesis that elevated levels of p53 protein may play a role in cellular senescence.
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“In the cell senescence process, two main proteins, a tumor suppressor protein and critical cell cycle regulator Retinoblastoma protein (Rb) and p53 tumor suppressor protein are activated; their inactivation prevented senescence (Kulju and Lehman 1995).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Kulju and Lehman 1995
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Background
Metadata
- Authors
- Kulju, K. S., & Lehman, J. M.
- Affiliations
- Albany Medical College (US)
- ORCID
- Lehman, John M.
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 1995-04
- Volume
- 217
- Issue
- 2
- Pages
- 336-345
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2062636398
- Cited by
- 155
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 8
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA-41608)
- 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, cellular senescence, cellular aging, human diploid fibroblasts, IMR-90 cells, p53 protein levels, p53 isoforms, tumor suppressor proteins
- MeSH terms
- Cell Cycle, Cell Line, Diploidy, Fibroblasts, Humans, RNA, Messenger, Electrophoresis, Gel, Two-Dimensional, Tumor Suppressor Protein p53, Cellular Senescence
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