ArticleProceedings of the National Academy of Sciences of the United States of America2016
E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- GSH-Responsive Nanoparticles Enhance Hepatocellular Carcinoma Immunotherapy Through Synergistic Effects of Cuproptosis and PI3K Inhibitor Combination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Pyruvate Dehydrogenase Complex: A 90-Year-Old Enigma Shaping the Future of Structural Enzymology.Advances in experimental medicine and biology · 2026Review
- Role and mechanisms of cuproptosis in the pathogenesis of Wilson's disease (Review).International journal of molecular medicine · 2025Review
- DLAT activates EMT to promote HCC metastasis by regulating GLUT1-mediated aerobic glycolysis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.Nature communications · 2025Article
- NF-κB factors cooperate with Su(Hw)/E4F1 to balance Drosophila/human immune responses via modulating dynamic expression of miR-210.Nucleic acids research · 2024Article
- MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function.Cell death & disease · 2023Article
- Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin.Nature communications · 2023Article
- Transcription factor E4F1 as a regulator of cell life and disease progression.Science advances · 2023Review
- Transcription factor E4F1 dictates spermatogonial stem cell fate decisions by regulating mitochondrial functions and cell cycle progression.Cell & bioscience · 2023Article
- Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Article
- m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency.Clinical and translational medicine · 2022Article
- Cuproptosis-related gene signature stratifies lower-grade glioma patients and predicts immune characteristics.Frontiers in genetics · 2022Article
- Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma.Frontiers in oncology · 2022Article
- A broad cuproptosis landscape in inflammatory bowel disease.Frontiers in immunology · 2022Article
- The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes.Nature communications · 2021Article
- Dietary interventions as regulators of stem cell behavior in homeostasis and disease.Genes & development · 2021Review
- Review
- Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis.
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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.