ArticleThe Journal of biological chemistry2014
New role for Kruppel-like factor 14 as a transcriptional activator involved in the generation of signaling lipids.
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 32 papers.
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Who cites it
32 citing papers in PubMed, 75 citations in OpenAlex.
- The KLF14 Variant is Associated with Type 2 Diabetes and HbABiochemical genetics · 2021Trial
- Enhancer of Zeste Homolog 2 Protects Mucosal Melanoma from Ferroptosis via the KLF14-SLC7A11 Signaling Pathway.Cancers · 2024Article
- KLF14 directly downregulates the expression of GPX4 to exert antitumor effects by promoting ferroptosis in cervical cancer.Journal of translational medicine · 2024Article
- Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning.BMC genomics · 2024Article
- Article
- Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms.Metabolites · 2023Review
- KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2.Journal of experimental & clinical cancer research : CR · 2023Article
- Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients.Frontiers in endocrinology · 2023Article
- Differential Genetic and Epigenetic Effects of theInternational journal of molecular sciences · 2022Article
- EZH2-mediated inhibition of KLF14 expression promotes HSCs activation and liver fibrosis by downregulating PPARγ.Cell proliferation · 2021Article
- KLF4 Inhibits the Differentiation of Goat Intramuscular Preadipocytes Through Targeting C/EBPβ Directly.Frontiers in genetics · 2021Article
- Klf9 is a key feedforward regulator of the transcriptomic response to glucocorticoid receptor activity.Scientific reports · 2020Article
- Transcription Factor KLF14 and Metabolic Syndrome.Frontiers in cardiovascular medicine · 2020Review
- Article
- Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Review
- The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer.International journal of biological sciences · 2019Article
- Fibroblast growth factor 10 (FGF10) promotes the adipogenesis of intramuscular preadipocytes in goat.Molecular biology reports · 2018Article
- Krüppel-like factors: Crippling and un-crippling metabolic pathways.JACC. Basic to translational science · 2018Article
- The KLF14 transcription factor regulates hepatic gluconeogenesis in mice.The Journal of biological chemistry · 2017Article
- Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms.JCI insight · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Sphingosine kinase 1 (SK1) is an FGF-inducible gene responsible for generation of sphingosine-1-phosphate, a critical lipid signaling molecule implicated in diverse endothelial cell functions. In this study, we identified SK1 as a target of the canonical FGF2/FGF receptor 1 activation pathway in endothelial cells and sought to identify novel transcriptional pathways that mediate lipid signaling. Studies using the 1.9-kb SK1 promoter and deletion mutants revealed that basal and FGF2-stimulated promoter activity occurred through two GC-rich regions located within 633 bp of the transcription start site. Screening for GC-rich binding transcription factors that could activate this site demonstrated that KLF14, a gene implicated in obesity and the metabolic syndrome, binds to this region. Congruently, overexpression of KLF14 increased basal and FGF2-stimulated SK1 promoter activity by 3-fold, and this effect was abrogated after mutation of the GC-rich sites. In addition, KLF14 siRNA transfection decreased SK1 mRNA and protein levels by 3-fold. Congruently, SK1 mRNA and protein levels were decreased in livers from KLF14 knock-out mice. Combined, luciferase, gel shift, and chromatin immunoprecipitation assays showed that KLF14 couples to p300 to increase the levels of histone marks associated with transcriptional activation (H4K8ac and H3K14ac), while decreasing repressive marks (H3K9me3 and H3K27me3). Collectively, the results demonstrate a novel mechanism whereby SK1 lipid signaling is regulated by epigenetic modifications conferred by KLF14 and p300. Thus, this is the first description of the activity and mechanisms underlying the function of KLF14 as an activator protein and novel regulator of lipid signaling.
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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.