ArticleMolecular and cellular biology2012
Acid ceramidase (ASAH1) represses steroidogenic factor 1-dependent gene transcription in H295R human adrenocortical cells by binding to the receptor.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1.Advances in biological regulation · 2026Review
- Screening of serum biomarkers in patients with PCOS through lipid omics and ensemble machine learning.PloS one · 2025Article
- Lethal Phenotype-Based Database Screening Identifies Ceramide as a Negative Regulator of Primitive Streak Formation.Stem cells (Dayton, Ohio) · 2023Article
- Targeting Ceramides and Adiponectin Receptors in the Islet of Langerhans for Treating Diabetes.Molecules (Basel, Switzerland) · 2022Review
- Acid ceramidase improves mitochondrial function and oxidative stress in Niemann-Pick type C disease by repressing STARD1 expression and mitochondrial cholesterol accumulation.Redox biology · 2021Article
- Article
- The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone.The Journal of endocrinology · 2019Review
- Mitochondrial Cholesterol in Alzheimer's Disease and Niemann-Pick Type C Disease.Frontiers in neurology · 2019Review
- Dose dependent actions of LCL521 on acid ceramidase and key sphingolipid metabolites.Bioorganic & medicinal chemistry · 2018Article
- Endogenous acid ceramidase protects epithelial cells from Porphyromonas gingivalis-induced inflammation in vitro.Biochemical and biophysical research communications · 2018Article
- Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease.Frontiers in physiology · 2017Review
- Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.Journal of assisted reproduction and genetics · 2015Article
- Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs.Bioorganic & medicinal chemistry · 2014Article
- Silencing diacylglycerol kinase-theta expression reduces steroid hormone biosynthesis and cholesterol metabolism in human adrenocortical cells.Biochimica et biophysica acta · 2014Article
- Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes.Advances in biological regulation · 2014Review
- cAMP-stimulated transcription of DGKθ requires steroidogenic factor 1 and sterol regulatory element binding protein 1.Journal of lipid research · 2013Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Adrenocorticotropin (ACTH) signaling increases glucocorticoid production by promoting the interaction of transcription factors and coactivator proteins with the promoter of steroidogenic genes. The nuclear receptor steroidogenic factor 1 (SF-1) is essential for steroidogenic gene transcription. Sphingosine (SPH) is a ligand for SF-1. Moreover, suppression of expression of acid ceramidase (ASAH1), an enzyme that produces SPH, increases the transcription of multiple steroidogenic genes. Given that SF-1 is a nuclear protein, we sought to define the molecular mechanisms by which ASAH1 regulates SF-1 function. We show that ASAH1 is localized in the nuclei of H295R adrenocortical cells and that cyclic AMP (cAMP) signaling promotes nuclear sphingolipid metabolism in an ASAH1-dependent manner. ASAH1 suppresses SF-1 activity by directly interacting with the receptor. Chromatin immunoprecipitation (ChIP) assays revealed that ASAH1 is recruited to the promoter of various SF-1 target genes and that ASAH1 and SF-1 colocalize on the same promoter region of the CYP17A1 and steroidogenic acute regulatory protein (StAR) genes. Taken together, these results demonstrate that ASAH1 is a novel coregulatory protein that represses SF-1 function by directly binding to the receptor on SF-1 target gene promoters and identify a key role for nuclear lipid metabolism in regulating gene transcription.
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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.