The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
5-Lipoxygenase regulates senescence-like growth arrest by promoting ROS-dependent p53 activation
Open accessAbstract
5-Lipoxygenase (5LO) is involved in the production of leukotrienes and reactive oxygen species (ROS) from arachidonic acid. Its strong activation has been associated with several diseases like cancer and neurodegeneration. Here we show that 5LO activity increases during senescence-like growth arrest induced by oncogenic ras or culture history in both human and mouse embryo fibroblasts. Overexpression of 5LO promotes senescence-like growth arrest via a p53/p21-dependent pathway, and this occurs independently of telomerase activity. 5LO stabilizes p53 through phosphorylation at Ser15 and increases expression of the p53-transcriptional target p21. This is achieved by regulating ROS production. Indeed, ROS are increased in 5LO-arrested cells. Antioxidants and a low oxygen environment prevent 5LO-induced growth arrest. Finally, 5LO inhibition reduces the growth arrest induced by oncogenic ras or culture history and these effects are neutralized by the addition of exogenous ROS. These data link the 5LO pathway to oxidative crises of primary fibroblast and suggest that the ability of 5LO to induce senescence-like growth arrest may be important in the pathogenesis of 5LO-associated disorders.
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“Ras-induced senescence can be inhibited by using antioxidants or growing cells in low-oxygen conditions (8, 25, 33, 51).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [8]
Experimental — accuracy not yet measuredIn the citing paper
“COX-2 inhibition similarly affected cell number, IL-6 secretion, EdU incorporation and colony formation in oncogenic RAS-induced senescent cells (Catalano et al., 2005; Serrano et al., 1997) (Figures S4B–S4F).”
From Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis (2021) · cites this paper as Catalano et al., 2005
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Metadata
- Authors
- Catalano, A., Rodilossi, S., Caprari, P., Coppola, V., & Procopio, A.
- Affiliations
- Marche Polytechnic University (IT)
- National Cancer Institute (US)
- Corresponding author
- Catalano, Alfonso
- Venue
- The EMBO Journal
- Published
- 2004-12-16
- Volume
- 24
- Issue
- 1
- Pages
- 170-179
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC544914
- OpenAlex
- W2068549027
- Cited by
- 123
- References
- 42
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- Fondazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- 5-lipoxygenase, reactive oxygen species, p53 activation, p21, oncogenic Ras, culture history, oxidative stress, leukotrienes, arachidonic acid metabolism, embryonic fibroblasts, antioxidant defense, 5-lipoxygenase inhibition
- MeSH terms
- Animals, Arachidonate 5-Lipoxygenase, Cell Survival, Cells, Cultured, Fibroblasts, Humans, Phosphorylation, Signal Transduction, Transcriptional Activation, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Cellular Senescence, Reactive Oxygen Species, Mice, Knockout, Telomerase, Cell Proliferation, Mice
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