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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Citations
Cites
1 retracted
Catalano, A., Caprari, P., Soddu, S., Procopio, A. D., & Romano, M. (2004) · The FASEB Journal · doi:10.1096/fj.04-2258fje · Cited by 39
RetractedOncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 6×
“…response to inadequate culture conditions or excessive mitogenic stimuli, cells respond with a program (i.e. stasis) that induces an irreversible growth arrest and is indistinguishable from replicative senescence in terms of morphological and molecular markers (Serrano et al, 1997; Schmitt, 2003).”
BackgroundMethodInfluentialAtmospheric carbon dioxide concentrations over the past 60 million years
Pearson, P. N., & Palmer, M. R. (2000) · Nature · doi:10.1038/35021000 · Cited by 1,771
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Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116
Post‐translational modifications and activation of p53 by genotoxic stresses
Appella, E., & Anderson, C. W. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02225.x · Cited by 1,095
PML regulates p53 acetylation and premature senescence induced by oncogenic Ras
Pearson, M. A., Carbone, R., Sebastiani, C., Cioce, M., Fagioli, M., Saito, S., Higashimoto, Y., Appella, E., Minucci, S., Pandolfi, P. P., et al. (2000) · Nature · doi:10.1038/35018127 · Cited by 869
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Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species
Lee, A. C., Fenster, B. E., Ito, H., Takeda, K., Bae, N. S., Hirai, T., Yu, Z.-X., Ferrans, V. J., Howard, B. H., & Finkel, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7936 · Cited by 691
Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis
D’Orazi, G., Cecchinelli, B., Bruno, T., Manni, I., Higashimoto, Y., Saito, S., Gostissa, M., Coen, S., Marchetti, A., Sal, G. D., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb714 · Cited by 682
Cited by
Sorted by citations
Items 101–122 of 122
Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer
Göbel, T., Goebel, B., Hyprath, M., Lamminger, I., Weisser, H., Angioni, C., Mathes, M., Thomas, D., & Kahnt, A. S. (2023) · Life Science Alliance · doi:10.26508/lsa.202201804 · Cited by 3
“This was accompanied by an activation of p53 by 5-LO–derived ROS resulting in the activation of p53 and thus p21 (Catalano et al, 2005).”
BackgroundZhang, H. (2012) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/rqhp-dj51 · Cited by 1
Stress factor – dependent differences in molecular mechanisms of premature cell senescence
Petrova, N. V., Velichko, A. K., Petrova, N. V., Razin, S. V., & Kantidze, O. L. (2015) · Biopolymers and Cell · doi:10.7124/bc.0008f4 · Cited by 1
The role of cellular lipid metabolism in aging
Chen, X., & Liu, J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95582-9.00013-9 · Cited by 2
Fatty acid desaturation controls cellular fate decisions between senescence and ferroptosis
Kuehnemann, C., Jezak, S. T., Mogck, B. A., Kura, N., Tariq, R., Che, Y., Vaittinen, M., Siokas, I., Deshpande, S., Guthrie, C., et al. (2026) · Cell · doi:10.1101/2024.10.03.616257 · Cited by 1
“For example, we and others have shown that oxylipin derivatives of AA and AdA can reinforce senescence 3,65,66 – so it remains possible that lowered levels of DGLA desaturation prevent the development of senescence via reduction of AA, rather than elimination of senescent cells by ferroptosis.”
BackgroundIntérêt des anti-oxydants dans l'alimentation des carnivores domestiques
Pastre, J., & Priymenko, N. (2007) · Revue Méd Vét · Cited by 1
Novel Therapeutic Targets for Ph+ Chromosome Leukemia and Its Leukemia Stem Cells: A Dissertation
Peng, C. (2010) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/c6dc-6x97
Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses
Bourdeau, V., & Ferbeyre, G. (2009) · Springer eBooks · doi:10.1007/978-1-4419-1075-2_3
Kregel, K. C., & Zhang, H. J. (2012)
Loss of Cdk5rap2 triggers cellular senescence via β-catenin-mediated downregulation of WIP1Preprint
Wang, X., Sipila, P., Si, Z., Rosales, J. L., Gao, X., & Lee, K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.09.194761
Data from Enhanced Antitumor Therapy by Inhibition of p21waf1 in Human Malignant Mesothelioma
Lazzarini, R., Moretti, S., Orecchia, S., Betta, P., Procopio, A., & Catalano, A. (2023) · doi:10.1158/1078-0432.c.6516796
Skinner, H. D., Sandulache, V. C., Ow, T. J., Meyn, R. E., Yordy, J. S., Beadle, B. M., Fitzgerald, A. L., Giri, U. P., Ang, K. K., & Myers, J. N. (2023) · doi:10.1158/1078-0432.c.6520878
Skinner, H. D., Sandulache, V. C., Ow, T. J., Meyn, R. E., Yordy, J. S., Beadle, B. M., Fitzgerald, A. L., Giri, U. P., Ang, K. K., & Myers, J. N. (2023) · doi:10.1158/1078-0432.c.6520878.v1
Data from Enhanced Antitumor Therapy by Inhibition of p21waf1 in Human Malignant Mesothelioma
Lazzarini, R., Moretti, S., Orecchia, S., Betta, P., Procopio, A., & Catalano, A. (2023) · doi:10.1158/1078-0432.c.6516796.v1
The resolvin D and E biogenesis pathway regulates senescence and ageingPreprint
Mira-Carnicer, M., Menendez-Garcia, M., Merino-Navarro, A., Palomino-Lozano, C., Anton-Barros, C., Palmero, I., Malaspina, A., Montesinos, J., & O’Loghlen, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.26.701588
de Freitas, J. A. N. L. F. (2020) · theses.fr (ABES) · doi:10.70675/0e6e3614z3915z4fb8za2cdz24b40b9679b2
Blue period - features of senescence 30 years after beta-galactosidase
Kuehnemann, C., & Wiley, C. D. (2026) · Aging · doi:10.18632/aging.206380
“Senescent cells display several features in common with ferroptosis, including increases in lipoxygenases [70, 71, 128], increased labile iron [102, 103, 129], and increased membrane-bound PUFA [129].”
Goenka, S. (2026) · Drug and Chemical Toxicology · doi:10.1080/01480545.2026.2726177
The Senescent Cell Induced Bystander Effect
Wordsworth, J. (2014)
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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