ArticleThe Journal of biological chemistry2014
E2F transcription factor 1 regulates cellular and organismal senescence by inhibiting Forkhead box O transcription factors.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
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- A natural variation-based screen in mouse cells reveals USF2 as a regulator of the DNA damage response and cellular senescence.G3 (Bethesda, Md.) · 2023Article
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- FOXOs: masters of the equilibrium.The FEBS journal · 2022Review
- PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process.Cellular and molecular life sciences : CMLS · 2022Review
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1.Frontiers in pharmacology · 2022Article
- E2F transcription factor 1 is involved in the phenotypic modulation of esophageal squamous cell carcinoma cells via microRNA-375.Bioengineered · 2021Article
- Combinatorial Approach UsingMolecules and cells · 2021Review
- m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer.Molecular therapy oncolytics · 2021Article
- Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021Review
- The Astrogenic Balance in the Aging Brain.Current neuropharmacology · 2021Review
- Comparative Transcriptomics Identifies Neuronal and Metabolic Adaptations to Hypergravity and Microgravity iniScience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
E2F1 and FOXO3 are two transcription factors that have been shown to participate in cellular senescence. Previous report reveals that E2F1 enhanced cellular senescence in human fibroblast cells, while FOXO transcription factors play against senescence by regulation reactive oxygen species scavenging proteins. However, their functional interplay has been unclear. Here we use E2F1 knock-out murine Embryonic fibroblasts (MEFs), knockdown RNAi constructs, and ectopic expression of E2F1 to show that it functions by negatively regulating FOXO3. E2F1 attenuates FOXO3-mediated expression of MnSOD and Catalase without affecting FOXO3 protein stability, subcellular localization, or phosphorylation by Akt. We mapped the interaction between E2F1 and FOXO3 to a region including the DNA binding domain of E2F1 and the C-terminal transcription-activation domain of FOXO3. We propose that E2F1 inhibits FOXO3-dependent transcription by directly binding FOXO3 in the nucleus and preventing activation of its target genes. Moreover, knockdown of the Caenorhabditis elegans E2F1 ortholog efl-1 significantly extends lifespan in a manner that requires the activity of the C. elegans FOXO gene daf-16. We conclude that there is an evolutionarily conserved signaling connection between E2F1 and FOXO3, which regulates cellular senescence and aging by regulating the activity of FOXO3. We speculate that drugs and/or therapies that inhibit this physical interaction might be good candidates for reducing cellular senescence and increasing longevity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.