ArticleAging cell2017
The PPARγ-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on p21-mediated cellular senescence.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Lactylation-driven KRT19 promotes non-small cell lung cancer progression by suppressing cellular senescence.Journal of experimental & clinical cancer research : CR · 2025Article
- Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Observational
- ADSCs attenuate Liver fibrosis via inducing HSC senescence: validation in dual-etiology models.PLoS neglected tropical diseases · 2025Article
- SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.Cell death & disease · 2024Article
- Urolithin A alleviates cell senescence by inhibiting ferroptosis and enhances corneal epithelial wound healing.Frontiers in medicine · 2024Article
- Article
- Roles for the methyltransferase SETD8 in DNA damage repair.Clinical epigenetics · 2022Review
- A cellular senescence-related genes model allows for prognosis and treatment stratification of hepatocellular carcinoma: A bioinformatics analysis and experimental verification.Frontiers in genetics · 2022Article
- B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway.Cell death & disease · 2021Article
- Identification and validation of three core genes in p53 signaling pathway in hepatitis B virus-related hepatocellular carcinoma.World journal of surgical oncology · 2021Article
- Article
- The NSD2/WHSC1/MMSET methyltransferase prevents cellular senescence-associated epigenomic remodeling.Aging cell · 2020Article
- The ubiquitin-specific protease USP17 prevents cellular senescence by stabilizing the methyltransferase SET8 and transcriptionally repressingThe Journal of biological chemistry · 2019Article
- Senescent cells in the development of cardiometabolic disease.Current opinion in lipidology · 2019Review
- Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue-Going Beyond Apoptosis Induction.Frontiers in oncology · 2019Review
- Quercetin protects against ox‑LDL‑induced injury via regulation of ABCAl, LXR‑α and PCSK9 in RAW264.7 macrophages.Molecular medicine reports · 2018Article
- Salidroside slows the progression of EA.hy926 cell senescence by regulating the cell cycle in an atherosclerosis model.Molecular medicine reports · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence is a permanent proliferative arrest triggered by genome instability or aberrant growth stresses, acting as a protective or even tumor-suppressive mechanism. While several key aspects of gene regulation have been known to program this cessation of cell growth, the involvement of the epigenetic regulation has just emerged but remains largely unresolved. Using a systems approach that is based on targeted gene profiling, we uncovered known and novel chromatin modifiers with putative link to the senescent state of the cells. Among these, we identified SETD8 as a new target as well as a key regulator of the cellular senescence signaling. Knockdown of SETD8 triggered senescence induction in proliferative culture, irrespectively of the p53 status of the cells; ectopic expression of this epigenetic writer alleviated the extent doxorubicin-induced cellular senescence. This repressive effect of SETD8 in senescence was mediated by directly maintaining the silencing mark H4K20me1 at the locus of the senescence switch gene p21. Further in support of this regulatory link, depletion of p21 reversed this SETD8-mediated cellular senescence. Additionally, we found that PPARγ acts upstream and regulates SETD8 expression in proliferating cells. Downregulation of PPARγ coincided with the senescence induction, while its activation inhibited the progression of this process. Viewed together, our findings delineated a new epigenetic pathway through which the PPARγ-SETD8 axis directly silences p21 expression and consequently impinges on its senescence-inducing function. This implies that SETD8 may be part of a cell proliferation checkpoint mechanism and has important implications in antitumor therapeutics.
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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.