ArticleThe Journal of biological chemistry2016
CerS6 Is a Novel Transcriptional Target of p53 Protein Activated by Non-genotoxic Stress.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Determinants of CBiomolecules · 2026Article
- An integrative approach to studying sphingolipid metabolism reveals p53 as a master regulator of the pathway.Journal of lipid research · 2026Article
- Metabolic regulation by p53: Implications for cancer therapy.Molecules and cells · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- Osteoarthritis Bone Marrow MSCs Retain Regenerative Competence and Chemokine Responsiveness for Drug-Based In Situ Tissue Engineering.Stem cells international · 2025Article
- The effects of restraint stress on ceramide metabolism disorders in the rat liver: the role of CerS6 in hepatocyte injury.Lipids in health and disease · 2024Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- Long- and very long-chain ceramides are predictors of acute kidney injury in patients with acute coronary syndrome: the PEACP study.Cardiovascular diabetology · 2023Article
- Association between abnormal lipid metabolism and tumor.Frontiers in endocrinology · 2023Review
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Article
- Sphingolipids in embryonic development, cell cycle regulation, and stemness - Implications for polyploidy in tumors.Seminars in cancer biology · 2022Review
- Comprehensive analysis of LASS6 expression and prognostic value in ovarian cancer.Journal of ovarian research · 2021Article
- CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation.Cancer science · 2021Article
- A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis.International journal of molecular sciences · 2021Review
- The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy.Cancers · 2021Review
- Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers.Frontiers in oncology · 2021Article
- Dietary Folic Acid Alters Metabolism of Multiple Vitamins in a CerS6- and Sex-Dependent Manner.Frontiers in nutrition · 2021Article
- Sphingolipids and the link between alcohol and cancer.Chemico-biological interactions · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Our previous study suggested that ceramide synthase 6 (CerS6), an enzyme in sphingolipid biosynthesis, is regulated by p53: CerS6 was elevated in several cell lines in response to transient expression of p53 or in response to folate stress, which is known to activate p53. It was not clear, however, whether CerS6 gene is a direct transcriptional target of p53 or whether this was an indirect effect through additional regulatory factors. In the present study, we have shown that the CerS6 promoter is activated by p53 in luciferase assays, whereas transcriptionally inactive R175H p53 mutant failed to induce the luciferase expression from this promoter. In vitro immunoprecipitation assays and gel shift analyses have further demonstrated that purified p53 binds within the CerS6 promoter sequence spanning 91 bp upstream and 60 bp downstream of the transcription start site. The Promo 3.0.2 online tool for the prediction of transcription factor binding sites indicated the presence of numerous putative non-canonical p53 binding motifs in the CerS6 promoter. Luciferase assays and gel shift analysis have identified a single motif upstream of the transcription start as a key p53 response element. Treatment of cells with Nutlin-3 or low concentrations of actinomycin D resulted in a strong elevation of CerS6 mRNA and protein, thus demonstrating that CerS6 is a component of the non-genotoxic p53-dependent cellular stress response. This study has shown that by direct transcriptional activation of CerS6, p53 can regulate specific ceramide biosynthesis, which contributes to the pro-apoptotic cellular response.
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Registered trials
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.