Tumor suppressors and oncogenes in cellular senescence
Abstract
Cyclin-dependent kinase inhibitors p16(INK4a), p21(Cip1), and p27(Kip1) are regarded as key effectors of cellular senescence. In this review, we describe three senescence-inducing pathways involving these inhibitors, namely, the p16(INK4a)/Rb pathway, the p19(ARF)/p53/p21(Cip1) pathway, and the PTEN/p27(Kip1) pathway. We emphasize the participation of tumor suppressors and oncogenes in the regulation of these senescence-inducing pathways. Finally, we discuss the impact of the Ras and Myc oncogenes on the above-mentioned pathways.
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Many normal cells senesce when they overexpress certain oncogenes, such as activated components of the RAS-RAF-MEK signaling cascade.
“In addition, many normal cells senesce when they overexpress certain oncogenes, such as activated components of the RAS-RAF-MEK signaling cascade (Bringold and Serrano, 2000; Lundberg et al., 2000; Narita and Lowe, 2004).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Bringold and Serrano, 2000
The two senescence pathways are governed by the gatekeeper tumor suppressor proteins p53 and pRB.
“These pathways are governed by the gatekeeper tumor suppressor proteins p53 and pRB (Bringold and Serrano, 2000; Lundberg et al., 2000; Campisi, 2001).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Bringold and Serrano, 2000
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References 73 · Cited by 379
- Authors
- Bringold, F., & Serrano, M.
- Affiliations
- Centro Nacional de Biotecnología (ES)
- Corresponding author
- Serrano, Manuel
- ORCID
- Serrano, Manuel
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 35
- Issue
- 3
- Pages
- 317-329
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1978120498
- Cited by
- 379
- References
- 73
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 12 · 2018: 19 · 2017: 7 · 2016: 13 · 2015: 10 · 2014: 19 · 2013: 11 · 2012: 22
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- 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
- cellular senescence, tumor suppressor, oncogenes, cyclin-dependent kinase inhibitors, p16INK4a, p21, p27, oncogenic Ras, MYC oncogene
- MeSH terms
- Animals, Enzyme Inhibitors, Humans, Microtubule-Associated Proteins, Oncogenes, Phosphoric Monoester Hydrolases, Proteins, Genes, ras, Genes, Tumor Suppressor, Genes, p53, Tumor Suppressor Protein p53, Retinoblastoma Protein, Genes, Retinoblastoma, Cyclins, Genes, myc, Cellular Senescence, Apoptosis, Cell Cycle Proteins, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Proteins, Tumor Suppressor Protein p14ARF, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, PTEN Phosphohydrolase
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